Tnfrsf9

Summary

Gene Symbol: Tnfrsf9
Description: tumor necrosis factor receptor superfamily, member 9
Alias: 4-1BB, A930040I11Rik, AA408498, AI325004, CDw137, Cd137, ILA, Ly63, 4-1BB ligand receptor, CD137 antigen, T-cell antigen 4-1BB, secreted CD137 antigen, tumor necrosis factor receptor superfamily member 9
Species: mouse

Top Publications

  1. ncbi Inducible T cell antigen 4-1BB. Analysis of expression and function
    K E Pollok
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202
    J Immunol 150:771-81. 1993
  2. ncbi Endogenous 4-1BB ligand plays a critical role in protection from influenza-induced disease
    Gloria H Y Lin
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    J Immunol 182:934-47. 2009
  3. doi The 4-1BB ligand and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling
    Jihyun Yang
    Department of Oromaxillofacial Infection and Immunity, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea
    Eur J Immunol 38:1598-609. 2008
  4. ncbi 4-1BB costimulation of effector T cells for adoptive immunotherapy of cancer: involvement of Bcl gene family members
    Hidde M Kroon
    Division of Surgical Oncology, Surgery Department, University of Michigan, Ann Arbor, MI 48109 0932, USA
    J Immunother 30:406-16. 2007
  5. ncbi IL-15-dependent induction of 4-1BB promotes antigen-independent CD8 memory T cell survival
    Gayle Pulle
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    J Immunol 176:2739-48. 2006
  6. ncbi 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1
    Hyeon Woo Lee
    Immunomodulation Research Center, University of Ulsan, Korea
    J Immunol 169:4882-8. 2002
  7. doi CD137 (4-1BB) deficiency reduces atherosclerosis in hyperlipidemic mice
    Hyung Jun Jeon
    Division of Life and Pharmaceutical Science, Ewha Womans University, Seoul, Korea
    Circulation 121:1124-33. 2010
  8. pmc Deficiency for costimulatory receptor 4-1BB protects against obesity-induced inflammation and metabolic disorders
    Chu Sook Kim
    Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea
    Diabetes 60:3159-68. 2011
  9. ncbi Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo
    Ryan A Wilcox
    Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
    Blood 103:177-84. 2004
  10. ncbi CD134 Costimulation Couples the CD137 Pathway to Induce Production of Supereffector CD8 T Cells That Become IL-7 Dependent
    Seung Joo Lee
    Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA
    J Immunol 179:2203-14. 2007

Scientific Experts

  • Carla Palma
  • Yonglian Sun
  • B R Blazar
  • Guoxing Zheng
  • Ian R Humphreys
  • Qiao Li
  • Atsuki Fukushima
  • Byoung S Kwon
  • Robert S Mittler
  • Seung Woo Lee
  • Beom K Choi
  • Tania H Watts
  • Dass S Vinay
  • Michael Croft
  • Lieping Chen
  • Young H Kim
  • Ryan A Wilcox
  • Dongsheng Jiang
  • Herbert Schwarz
  • Jung D Kim
  • Kyung Ok Nam
  • Gloria H Y Lin
  • Anthony T Vella
  • Hyeon Woo Lee
  • Rajesh K Sharma
  • Junichiro Irie
  • Jun Wang
  • Chu Sook Kim
  • Seung Joo Lee
  • Zhe Shao
  • Chang H Kim
  • Koji Tamada
  • Laurent Sabbagh
  • Asis Palazon
  • Thai Hien Tu
  • Holbrook E Kohrt
  • Rina Yu
  • Teruo Kawada
  • Juergen Foell
  • Gefeng Zhu
  • Ryoko Hamano
  • Kirsten Eckstrum
  • Qianqiao Tang
  • Vaiva Vezys
  • Su K Seo
  • Shaqireen Kwajah M M
  • Hyung Jun Jeon
  • Myoung J Lee
  • J T Tan
  • Rich Henry Schabowsky
  • Haval Shirwan
  • Esma S Yolcu
  • Hong Zhao
  • Kutlu G Elpek
  • Dallas B Flies
  • Andrei I Chapoval
  • Rafi Ahmed
  • Byung Sam Kim
  • Suman Bandyopadhyay
  • Shelly J Robertson
  • Dong Hyeon Kim
  • Jihyun Yang
  • Young Jun Kang
  • Koh Hei Sonoda
  • Steven Seaman
  • Hilde Cheroutre
  • Benyue Zhang
  • Yunji Park
  • Yuwen Zhu
  • Hidde M Kroon
  • Leen Moens
  • Yuehong Wu
  • William M Ridgway
  • P Maerten
  • Gayle Pulle
  • Su Mi Shin
  • Camilo Cuadros
  • Jae H Choi
  • Jenny Hendriks
  • Jennifer L Cannons
  • Hajime Nishimoto
  • Seong A Ju
  • Woo J Kang
  • Edward M Bertram
  • Kan Saito
  • Ping Ying Pan
  • Manuela Flórido
  • Wojciech Dawicki
  • Gerald P Morris
  • Zheng Qi Wu

Detail Information

Publications99

  1. ncbi Inducible T cell antigen 4-1BB. Analysis of expression and function
    K E Pollok
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202
    J Immunol 150:771-81. 1993
    ..Cross-linking of 4-1BB on anti-CD3-stimulated T cells with 53A2 resulted in a dramatic enhancement of T cell proliferation. This suggests that 4-1BB may function as an accessory signaling molecule during T cell activation...
  2. ncbi Endogenous 4-1BB ligand plays a critical role in protection from influenza-induced disease
    Gloria H Y Lin
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    J Immunol 182:934-47. 2009
    ....
  3. doi The 4-1BB ligand and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling
    Jihyun Yang
    Department of Oromaxillofacial Infection and Immunity, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea
    Eur J Immunol 38:1598-609. 2008
    ....
  4. ncbi 4-1BB costimulation of effector T cells for adoptive immunotherapy of cancer: involvement of Bcl gene family members
    Hidde M Kroon
    Division of Surgical Oncology, Surgery Department, University of Michigan, Ann Arbor, MI 48109 0932, USA
    J Immunother 30:406-16. 2007
    ..in vitro costimulation of murine MCA 205 tumor-draining lymph node (TDLN) cells through a third signal, 4-1BB (CD137), in addition to CD3 and CD28 engagement significantly increases T-cell yield and amplifies antitumor responses in ..
  5. ncbi IL-15-dependent induction of 4-1BB promotes antigen-independent CD8 memory T cell survival
    Gayle Pulle
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    J Immunol 176:2739-48. 2006
    ..These data suggest a model whereby 4-1BB expression on memory CD8+ T cells, perhaps due to encounter with IL-15 in the bone marrow, allows 4-1BB/4-1BBL interactions to maintain memory CD8 T cell survival in the absence of Ag...
  6. ncbi 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1
    Hyeon Woo Lee
    Immunomodulation Research Center, University of Ulsan, Korea
    J Immunol 169:4882-8. 2002
    ..The results suggest a role for the antiapoptotic activities of Bcl-x(L) and Bfl-1 proteins in 4-1BB-mediated CD8(+) T cell survival in vivo...
  7. doi CD137 (4-1BB) deficiency reduces atherosclerosis in hyperlipidemic mice
    Hyung Jun Jeon
    Division of Life and Pharmaceutical Science, Ewha Womans University, Seoul, Korea
    Circulation 121:1124-33. 2010
    ..b>CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily, has been reported to be expressed in human ..
  8. pmc Deficiency for costimulatory receptor 4-1BB protects against obesity-induced inflammation and metabolic disorders
    Chu Sook Kim
    Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea
    Diabetes 60:3159-68. 2011
    ..As a member of the tumor necrosis factor receptor superfamily (TNFRSF9) expressed on immune cells, 4-1BB/CD137 provides a bidirectional inflammatory signal through binding to its ..
  9. ncbi Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo
    Ryan A Wilcox
    Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
    Blood 103:177-84. 2004
    ..We show here that administration of an agonistic monoclonal antibody (mAb) to CD137, a member of the tumor necrosis factor receptor superfamily, prevents the induction of CD8+ cytolytic T-lymphocyte ..
  10. ncbi CD134 Costimulation Couples the CD137 Pathway to Induce Production of Supereffector CD8 T Cells That Become IL-7 Dependent
    Seung Joo Lee
    Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA
    J Immunol 179:2203-14. 2007
    The TNFR superfamily members 4-1BB (CD137) and OX40 (CD134) are costimulatory molecules that potently boost CD8 and CD4 T cell responses...
  11. ncbi During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion
    Jenny Hendriks
    Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Immunol 175:1665-76. 2005
    ..Our data argue that ligand on dendritic cells and/or B cells may be critical for this...
  12. ncbi 4-1BB (CD137) controls the clonal expansion and survival of CD8 T cells in vivo but does not contribute to the development of cytotoxicity
    David Cooper
    Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Eur J Immunol 32:521-9. 2002
    ..These findings demonstrate that 4-1BB contributes to clonal expansion, survival, and development of Tc1 cells when protein antigen is encountered by primary CD8 T cells in an inflammatory environment in vivo...
  13. pmc Immune suppression or enhancement by CD137 T cell costimulation during acute viral infection is time dependent
    Benyue Zhang
    Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA
    J Clin Invest 117:3029-41. 2007
    b>CD137 is expressed on activated T cells and ligands to this costimulatory molecule have clinical potential for amplifying CD8 T cell immunity to tumors and viruses, while suppressing CD4 autoimmune T cell responses...
  14. ncbi 4-1BB costimulation enhances HSV-1-specific CD8+ T cell responses by the induction of CD11c+CD8+ T cells
    Young H Kim
    The Immunomodulation Research Center, University of Ulsan, Ulsan 680 749, Republic of Korea
    Cell Immunol 238:76-86. 2005
    ..Our studies demonstrated that 4-1BB stimulation enhanced both primary and memory anti-HSV-1 CD8+ T cell responses, which was mediated by a massive expansion of antigen-specific CD11c+CD8+ T cells...
  15. ncbi A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8 T cell response to influenza in vivo
    Edward M Bertram
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    J Immunol 172:981-8. 2004
    ..The results indicate that anti-4-1BB or 4-1BBL therapy will be most effective during the boost phase of a prime-boost vaccination strategy...
  16. ncbi Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis
    Su K Seo
    Immunomodulation Research Center, University of Ulsan, Ulsan, Korea
    J Immunol 171:576-83. 2003
    ..1/5.2, in order of abundance). Analysis of cell surface phenotypes showed that the failure to develop HSK in the 4-1BB(-/-) mice was associated with a reduced expression of CD62L at the time of T cell migration into the corneal stroma...
  17. ncbi Functional dichotomy between OX40 and 4-1BB in modulating effector CD8 T cell responses
    Seung Woo Lee
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    J Immunol 177:4464-72. 2006
    ..OX40 can positively regulate effector function and late accumulation/survival, whereas 4-1BB can initially operate in a negative manner to limit primary CD8 responses...
  18. pmc Species difference of CD137 ligand signaling in human and murine monocytes
    Qianqiao Tang
    Department of Physiology, and Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    PLoS ONE 6:e16129. 2011
    Stimulation of CD137 ligand on human monocytes has been shown to induce DC differentiation, and these CD137L-DCs are more potent than classical DCs, in stimulating T cell responses in vitro...
  19. pmc Tumor necrosis factor receptor subfamily 9 (Tnfrsf9) gene is expressed in distinct cell populations in mouse uterus and conceptus during implantation period of pregnancy
    Kirsten Eckstrum
    Department of Physiology, Southern Illinois University School of Medicine, Carbondale, 62901, IL, USA
    Cell Tissue Res 344:567-76. 2011
    Tumor necrosis factor receptor subfamily 9 (TNFRSF9) plays a potentially important general role in immune function. Tnfrsf9 gene expression has previously been characterized in late pregnant mouse uterus and placenta...
  20. doi 4-1BB signaling synergizes with programmed death ligand 1 blockade to augment CD8 T cell responses during chronic viral infection
    Vaiva Vezys
    Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA
    J Immunol 187:1634-42. 2011
    ..These findings demonstrate the importance of carefully manipulating the balance between activating and inhibitory signals to enhance T cell responses during chronic infection...
  21. doi Leukocyte-specific protein 1 links TNF receptor-associated factor 1 to survival signaling downstream of 4-1BB in T cells
    Laurent Sabbagh
    Maisonneuve Rosemont Hospital Research Centre, Montreal, Quebec, Canada
    J Leukoc Biol 93:713-21. 2013
    ..Collectively, our work shows that TRAF1 and LSP1 cooperate downstream of 4-1BB to activate ERK signaling and down-modulate the levels of Bim leading to enhanced T cell survival...
  22. doi The HIF-1α hypoxia response in tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy
    Asis Palazon
    CIMA and CUN University of Navarra, Pamplona, Navarra, Spain
    Cancer Discov 2:608-23. 2012
    ..T lymphocytes (TIL) of transplanted colon carcinomas, melanomas, and spontaneous breast adenocarcinomas are CD137 (4-1BB)-positive, as opposed to their counterparts in tumor-draining lymph nodes and spleen...
  23. ncbi CD137 induces proliferation of murine hematopoietic progenitor cells and differentiation to macrophages
    Dongsheng Jiang
    Department of Physiology, and Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    J Immunol 181:3923-32. 2008
    b>CD137 is a member of the TNFR family, and reverse signaling through the CD137 ligand, which is expressed as a cell surface transmembrane protein, costimulates or activates APCs...
  24. doi Regulation of mouse 4-1BB expression: multiple promoter usages and a splice variant
    Jung D Kim
    Biomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Korea
    Mol Cells 31:141-9. 2011
    ..The splicing variant was highly induced by TCR stimulation. Our results reveal 4-1BB also has a negative regulation system through soluble 4-1BB produced from a splice variant induced under activation conditions...
  25. doi 4-1BB triggering ameliorates experimental autoimmune encephalomyelitis by modulating the balance between Th17 and regulatory T cells
    Young H Kim
    Immune and Cell Therapy Branch, Division of Cancer Biology, National Cancer Center, Goyang si, Gyeongi do 410 769, Korea
    J Immunol 187:1120-8. 2011
    ....
  26. ncbi The 4-1BB costimulation augments the proliferation of CD4+CD25+ regulatory T cells
    Guoxing Zheng
    Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA
    J Immunol 173:2428-34. 2004
    ..These results support the notion that the peripheral expansion of the CD4(+)CD25(+) T cells is controlled in part by costimulation...
  27. ncbi 4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells
    Beom K Choi
    Immunomodulation Research Center, University of Ulsan, Korea
    J Leukoc Biol 75:785-91. 2004
    4-1BB (CD137) is a costimulatory molecule involved in the activation and survival of CD4, CD8, and natural killer cells...
  28. ncbi Immune responses in 4-1BB (CD137)-deficient mice
    Byoung S Kwon
    Immunomodulation Research Center, University of Ulsan, Ulsan, Korea
    J Immunol 168:5483-90. 2002
    ..The in vitro expression of 4-1BB (CD137) is induced following activation of T cells with various stimuli, including anti-TCR mAbs, lectins, and a ..
  29. ncbi In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses
    E Scott Halstead
    Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, PA, USA
    Nat Immunol 3:536-41. 2002
    ..We found that in vivo CD137 stimulation with an agonistic monoclonal antibody enhanced the primary CD8+ T cell response to influenza type A ..
  30. ncbi 4-1BB-like molecule is expressed in islet-infiltrating mononuclear cells and in the gray matter of the brain
    Ho Y Lim
    The Immunomodulation Research Center and Department of Biological Sciences, University of Ulsan, Ulsan, 680 749, Korea
    Cell Biol Int 26:271-8. 2002
    ..The staining pattern strongly resembled the receptor/nerve terminals in the brain and in the peripheral nervous system. Taken together, BBLP may be associated with the early phase of inflammation and with brain function...
  31. ncbi A mRNA variant encoding a soluble form of 4-1BB, a member of the murine NGF/TNF receptor family
    M Setareh
    Sam and Rose Stein Institute for Research on Aging, University of California at San Diego, La Jolla 92093 0663, USA
    Gene 164:311-5. 1995
    ..These results identify a novel form of 4-1BB. This and the previously known membrane-associated form have a broad tissue distribution, suggesting a more diverse role in host defense...
  32. ncbi Cutting edge: Expression of functional CD137 receptor by dendritic cells
    Ryan A Wilcox
    Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
    J Immunol 168:4262-7. 2002
    ..We report in this work that freshly isolated mouse splenic DCs and bone marrow-derived DCs express CD137 on the cell surface and in soluble form. Triggering CD137 increased the secretion of IL-6 and IL-12 from DCs...
  33. pmc Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors
    Ryan A Wilcox
    Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Clin Invest 109:651-9. 2002
    ..previously that established tumors in mice receiving an agonistic mAb to the T cell costimulatory molecule 4-1BB (CD137) regress due to enhanced tumor antigen-specific cytotoxic T lymphocyte responses...
  34. ncbi Molecular and biological characterization of human 4-1BB and its ligand
    M R Alderson
    Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle, WA 98101
    Eur J Immunol 24:2219-27. 1994
    ..In contrast, ligation of 4-1BB on T cell clones enhanced activation-induced cell death when triggered by engagement of the TCR/CD3 complex...
  35. doi Characterisation of soluble murine CD137 and its association with systemic lupus
    Zhe Shao
    Department of Physiology, and Immunology Programme, Yong Loo Lin School of Medicine, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore
    Mol Immunol 45:3990-9. 2008
    b>CD137 is a member of the tumor necrosis factor receptor family, and is involved in the regulation of activation, proliferation, differentiation and apoptosis of T cells, B cells, monocytes, dendritic cells, natural killer cells and ..
  36. pmc Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells
    Seung Woo Lee
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    Nat Immunol 9:917-26. 2008
    ..Thus, 4-1BB and 4-1BBL have a previously unknown function in limiting myelopoiesis and the development of dendritic cells...
  37. ncbi Modulating protective and pathogenic CD4+ subsets via CD137 in type 1 diabetes
    Junichiro Irie
    Division of Rheumatology and Immunology, University of Pittsburgh School of Medicine, PA, USA
    Diabetes 56:186-96. 2007
    CD137 (TNFRSF9) is an activation-inducible T-cell costimulatory molecule and a member of the tumor necrosis factor (TNF) receptor superfamily. Cd137 is also a candidate gene (in the Idd9.3 interval) for autoimmune diabetes in NOD mice...
  38. ncbi Enhanced CD4 T cell responsiveness in the absence of 4-1BB
    Seung Woo Lee
    La Jolla Institute for Allergy and Immunology, Division of Molecular Immunology, San Diego, CA 92121, USA
    J Immunol 174:6803-8. 2005
    The 4-1BB (CD137) is a member of the TNFR superfamily, and is expressed on several cell types, including activated T cells...
  39. ncbi Genetic and functional association of the immune signaling molecule 4-1BB (CD137/TNFRSF9) with type 1 diabetes
    Jennifer L Cannons
    Department of Immunology, 1 King s College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada
    J Autoimmun 25:13-20. 2005
    ..These data provide evidence in support of Idd9.3 as the locus encoding 4-1BB and suggest that the 4-1BB signaling pathway could have a primary function in the etiology of autoimmune disease...
  40. ncbi 4-1BB-specific monoclonal antibody promotes the generation of tumor-specific immune responses by direct activation of CD8 T cells in a CD40-dependent manner
    Robert E Miller
    Department of Cancer Biology, Immunex Research and Development, Seattle, WA 98101, USA
    J Immunol 169:1792-800. 2002
    4-1BB (CD137) is a member of the TNFR superfamily (TNFRSF9). T cell expression of 4-1BB is restricted to activated cells, and cross-linking has been shown to deliver a costimulatory signal...
  41. ncbi Cell surface 4-1BBL mediates sequential signaling pathways 'downstream' of TLR and is required for sustained TNF production in macrophages
    Young Jun Kang
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Immunol 8:601-9. 2007
    ..Our results indicate that two different TLR4 complexes sequentially form and selectively control early and late TNF production...
  42. ncbi Infection-induced up-regulation of the costimulatory molecule 4-1BB in osteoblastic cells and its inhibitory effect on M-CSF/RANKL-induced in vitro osteoclastogenesis
    Kan Saito
    Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1 7 1 Sakamoto, Nagasaki 852 8588, Japan
    J Biol Chem 279:13555-63. 2004
    ..A gene encoding 4-1BB (CD137), a member of the tumor necrosis factor-alpha receptor family, was found to be one of the up-regulated genes...
  43. pmc cDNA sequences of two inducible T-cell genes
    B S Kwon
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46223
    Proc Natl Acad Sci U S A 86:1963-7. 1989
    ..Both peptides contain putative leader sequences. The protein encoded by 4-1BB also has a potential membrane anchor segment and other features also seen in known receptor proteins...
  44. pmc T-cell activation molecule 4-1BB binds to extracellular matrix proteins
    N J Chalupny
    Bristol Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121
    Proc Natl Acad Sci U S A 89:10360-4. 1992
    ..These results suggest that carbohydrates may play a role in mediating the 4-1BB-extracellular matrix protein adhesion...
  45. ncbi Signaling through NK cell-associated CD137 promotes both helper function for CD8+ cytolytic T cells and responsiveness to IL-2 but not cytolytic activity
    Ryan A Wilcox
    Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
    J Immunol 169:4230-6. 2002
    ..In fact, the generation of antitumor immunity by the administration of an agonistic mAb against CD137 is NK cell-dependent...
  46. doi CD137 ligand signaling induces human monocyte to dendritic cell differentiation
    Shaqireen Kwajah M M
    Department of Physiology and Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    Eur J Immunol 40:1938-49. 2010
    The ligand for CD137 (4-1BB) is expressed on peripheral human monocytes and delivers a potent activating signal via reverse signaling...
  47. ncbi Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor
    R G Goodwin
    Immunex Research and Development Corporation, Seattle, WA 98101
    Eur J Immunol 23:2631-41. 1993
    ..Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB...
  48. pmc In vivo accumulation of T cells in response to IL-2/anti-IL-2 mAb complexes is dependent in part on the TNF family ligand 4-1BBL
    Gloria H Y Lin
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    Immunol Cell Biol 90:743-7. 2012
    ..These effects were independent of IL-2-induced cell division, suggesting that 4-1BBL-induced survival signals contribute to IL-2/mAb-complex-induced T-cell accumulation in vivo...
  49. pmc 4-1BB/4-1BBL interaction promotes obesity-induced adipose inflammation by triggering bidirectional inflammatory signaling in adipocytes/macrophages
    Thai Hien Tu
    Department of Food Science and Nutrition, University of Ulsan, Ulsan, Republic of Korea
    Mediators Inflamm 2012:972629. 2012
    ..These findings indicate that 4-1BB/4-1BBL-mediated bidirectional signaling in adipocytes/macrophages promotes adipose inflammation. 4-1BB and 4-1BBL may be useful targets for protection against obesity-induced adipose inflammation...
  50. pmc Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer
    Holbrook E Kohrt
    Department of Medicine, Division of Oncology, Stanford University, Stanford, California, USA
    J Clin Invest 122:1066-75. 2012
    ..HER2-overexpressing breast cancer cells, human NK cells become activated and express the costimulatory receptor CD137. CD137 activation, which was dependent on NK cell expression of the FcγRIII receptor, occurred both in vitro and ..
  51. pmc Adjuvant effect of anti-4-1BB mAb administration in adoptive T cell therapy of cancer
    Qiao Li
    Division of Surgical Oncology, University of Michigan, Ann Arbor, MI 48109 5932, USA
    Int J Biol Sci 3:455-62. 2007
    ....
  52. ncbi NKT cell-derived urokinase-type plasminogen activator promotes peripheral tolerance associated with eye
    Koh Hei Sonoda
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 179:2215-22. 2007
    ..In conclusion, uPA derived from iNKT cells is required to induce peripheral tolerance via the eye...
  53. ncbi 4-1BB engagement costimulates NKT cell activation and exacerbates NKT cell ligand-induced airway hyperresponsiveness and inflammation
    Dong Hyeon Kim
    Laboratory of Immunology and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shillim 9 Dong, Kwanak gu, Seoul, Republic of Korea
    J Immunol 180:2062-8. 2008
    Multiple studies have demonstrated that 4-1BB (CD137), a member of the TNF receptor superfamily, is expressed on several immune cells including activated T cells...
  54. ncbi Distinct approaches to investigate the importance of the murine 4-1BB 4-1BBL interaction in the antibody response to Streptococcus pneumoniae
    Leen Moens
    Department of Molecular Cell Biology, Faculty of Medicine, Catholic University Leuven, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
    J Leukoc Biol 82:638-44. 2007
    ..The 4-1BB-4-1BBL interaction is not involved in the antibody response to soluble caps-PS. The influence of the 4-1BB-4-1BBL interaction in the immune reaction to S. pneumoniae Serotype 3 depends on the experimental system used...
  55. ncbi Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses
    Juyang Kim
    The Immunomodulation Research Center, University of Ulsan, Ulsan 680 749, Korea
    Exp Mol Med 35:509-17. 2003
    ..Overall, our results demonstrate the involvement of 4-1BB in CD4(+) Th1 cell responses by regulating the clonal expansion and survival of CD4(+) T cells as seen in CD8(+) T cells...
  56. pmc Role of endogenous 4-1BB in the development of systemic lupus erythematosus
    Dass S Vinay
    LSU Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA, USA
    Immunology 122:394-400. 2007
    ..These data suggest that the 4-1BB-4-1BB ligand signalling pathway plays an important role in SLE and that deletion of 4-1BB confers susceptibility to lpr mice, leading to accelerated induction of disease and early mortality...
  57. pmc CD137 costimulation of CD8+ T cells confers resistance to suppression by virus-induced regulatory T cells
    Shelly J Robertson
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
    J Immunol 180:5267-74. 2008
    ..In this study, we demonstrate that immunotherapy with a combination of agonistic anti-CD137 Ab and virus-specific, TCR-transgenic CD8(+) T cells produced greater than 99% reductions of virus levels within 2 ..
  58. pmc CD137-mediated pathogenesis from chronic hepatitis to hepatocellular carcinoma in hepatitis B virus-transgenic mice
    Jun Wang
    Key Laboratory of Infection and Immunity, Institute of Biophysics, Graduate University, Chinese Academy of Sciences, Beijing, China
    J Immunol 185:7654-62. 2010
    ..We report in this article that repetitive infusion of anti-CD137 agonist mAb in HBV-transgenic mice closely mimics this process by sequentially inducing hepatitis, fibrosis, ..
  59. pmc 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB
    R H Arch
    Department of Medicine, Howard Hughes Medical Institute, The University of Chicago, Illinois 60637, USA
    Mol Cell Biol 18:558-65. 1998
    ..Taken together, our results indicate that 4-1BB and Ox40 bind TRAF proteins to initiate a signaling cascade leading to activation of nuclear factor kappaB...
  60. pmc Self-antigen prevents CD8 T cell effector differentiation by CD134 and CD137 dual costimulation
    Suman Bandyopadhyay
    Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030 1601, USA
    J Immunol 181:7728-37. 2008
    ....
  61. pmc 4-1BB functions as a survival factor in dendritic cells
    Beom K Choi
    R and D Center for Cancer Therapeutics, National Cancer Center, Ilsan, Korea
    J Immunol 182:4107-15. 2009
    4-1BB (CD137) is expressed on dendritic cells (DCs) and its biological function has remained largely unresolved...
  62. pmc 4-1BB ligand as an effective multifunctional immunomodulator and antigen delivery vehicle for the development of therapeutic cancer vaccines
    Rajesh K Sharma
    Department of Microbiology and Immunology, James Brown Cancer Center, Institute for Cellular Therapeutics, University of Louisville and ApoImmune, Inc, Louisville, Kentucky, USA
    Cancer Res 70:3945-54. 2010
    ....
  63. pmc TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40
    Ryoko Hamano
    Laboratory of Molecular Immunoregulation, Cancer Inflammation Program, Center for Cancer Research, NCI Frederick, Frederick, MD 21702 1201, USA
    Eur J Immunol 41:2010-20. 2011
    ....
  64. ncbi 4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination
    J T Tan
    The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 164:2320-5. 2000
    ..In an effort to understand what factors can improve immune responses to peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since 4-1BB has been shown to promote T cell responses in other systems...
  65. ncbi Regulation of dendritic cell function by NK cells: mechanisms underlying the synergism in the combination therapy of IL-12 and 4-1BB activation
    Ping Ying Pan
    Carl C Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Immunol 172:4779-89. 2004
    ....
  66. ncbi 4-1BB enhances CD8+ T cell expansion by regulating cell cycle progression through changes in expression of cyclins D and E and cyclin-dependent kinase inhibitor p27kip1
    Hyeon Woo Lee
    Immunomodulation Research Center, University of Ulsan, Ulsan, Korea
    Eur J Immunol 33:2133-41. 2003
    ..Our results suggest a role for cyclin D2, D3, and E, and p27(kip1) proteins in the 4-1BB-mediated cell cycle progression of CD8(+) T cells in vivo...
  67. pmc Involvement of 4-1BB (CD137)-4-1BBligand interaction in the modulation of CD4 T cell-mediated inflammatory colitis
    P Maerten
    Laboratory of Experimental Immunology, University Hospital, Katholieke Universiteit Leuven, Belgium
    Clin Exp Immunol 143:228-36. 2006
    ..In conclusion, our data provide evidence that 4-1BB-4-1BBL interaction modulates the effector CD4+ T cell-driven immune response and cytokine production in experimental colitis without affecting regulatory T cell function...
  68. pmc Regulation of granulocyte and macrophage populations of murine bone marrow cells by G-CSF and CD137 protein
    Dongsheng Jiang
    Department of Physiology, and Immunology Programme, Yong Loo Lin School of Medicine, Singapore, Singapore
    PLoS ONE 5:e15565. 2010
    ..Granulocyte colony-stimulating factor (G-CSF) and CD137 (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte and macrophage survival and differentiation, ..
  69. ncbi Role of 4-1BB in allograft rejection mediated by CD8+ T cells
    Jun Wang
    Emory Transplant Center and the Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
    Am J Transplant 3:543-51. 2003
    ..4-1BB (CD137) has been shown to be an important regulatory molecule for CD8+ T cells in a variety of nontransplant models...
  70. ncbi Immunity to melanoma mediated by 4-1BB is associated with enhanced activity of tumour-infiltrating lymphocytes
    Seong A Ju
    Immunomodulation Research Center, University of Ulsan, Ulsan, Korea
    Immunol Cell Biol 83:344-51. 2005
    4-1BB costimulates T cells to carry out effector functions such as eradication of established tumours. 4-1BB (CD137) is a member of the TNF receptor family, and its triggering by either 4-1BB ligand or antibody ligation induces T-cell ..
  71. pmc Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptor
    Hajime Nishimoto
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr, San Diego, CA 92121, USA
    Blood 106:4241-8. 2005
    ..Therefore, FcepsilonRI-inducible 4-1BB plays a costimulatory function together with FcepsilonRI stimulation...
  72. ncbi Cross-linking of 4-1BB up-regulates IL-13 expression in CD8(+) T lymphocytes
    Kyung Ok Nam
    The Immunomodulation Research Center and Graduate Program in Immunology and Biomedicine, University of Ulsan, Ulsan 680 749, South Korea
    Cytokine 33:87-94. 2006
    ....
  73. pmc Genes that distinguish physiological and pathological angiogenesis
    Steven Seaman
    Tumor Angiogenesis Section, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA
    Cancer Cell 11:539-54. 2007
    ..These studies reveal striking differences between physiological and pathological angiogenesis potentially important for the development of tumor-specific, vascular-targeted therapies...
  74. ncbi Inhibition of Th2-mediated allergic airway inflammatory disease by CD137 costimulation
    Yonglian Sun
    Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 177:814-21. 2006
    The engagement of CD137 (4-1BB), an inducible T cell costimulatory receptor and member of the TNF receptor superfamily, by agonistic Abs can promote strong tumor and viral immunity mediated by CD8(+) T cells and stimulate IFN-gamma ..
  75. ncbi In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway
    Linda Diehl
    Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 168:3755-62. 2002
    ..The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers...
  76. ncbi Amelioration of mercury-induced autoimmunity by 4-1BB
    Dass S Vinay
    Louisiana State University Eye Center, Louisiana State University Health Science Center School of Medicine, New Orleans, LA 70112, USA
    J Immunol 177:5708-17. 2006
    ....
  77. pmc CD137 stimulation delivers an antigen-independent growth signal for T lymphocytes with memory phenotype
    Yuwen Zhu
    Department of Dermatology, Johns Hopkins University School of Mediicne, 1550 Orleans Street, Baltimore, MD 21231, USA
    Blood 109:4882-9. 2007
    b>CD137 has long been recognized as a costimulatory receptor for growth and functional maturation of recently activated T cells in the presence of T-cell receptor signal...
  78. ncbi Genomic organization and chromosomal localization of the T-cell antigen 4-1BB
    B S Kwon
    Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202
    J Immunol 152:2256-62. 1994
    ..A comparison of exon-intron organization among the genes of the nerve growth factor receptor family indicated that most C6 motif is interrupted by an intron...
  79. ncbi ILA, the human 4-1BB homologue, is inducible in lymphoid and other cell lineages
    H Schwarz
    Sam and Rose Stein Institute for Research on Aging, San Diego, La Jolla, CA
    Blood 85:1043-52. 1995
    We recently identified a gene that is induced by lymphocyte activation (ILA). The sequence of the full-length 1...
  80. ncbi Vaccination with dendritic cells pulsed with apoptotic tumors in combination with anti-OX40 and anti-4-1BB monoclonal antibodies induces T cell-mediated protective immunity in Her-2/neu transgenic mice
    Camilo Cuadros
    Sidney Kimmel Cancer Center, San Diego, CA 92121, USA
    Int J Cancer 116:934-43. 2005
    ....
  81. ncbi A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family
    H Schwarz
    Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093 0663
    Gene 134:295-8. 1993
    ..The gene encodes three cysteine-rich motifs in the extracellular domain which are characteristic of this receptor family, a transmembrane region and a short N-terminal cytoplasmic portion which contains potential phosphorylation sites...
  82. ncbi High-resolution mapping of the genes Kcnb3 and Ly63 on distal mouse chromosome 4
    M P Coleman
    Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK
    Mamm Genome 7:552-3. 1996
  83. pmc Hypercostimulation through 4-1BB distorts homeostasis of immune cells
    Seung Woo Lee
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
    J Immunol 182:6753-62. 2009
    ....
  84. ncbi 4-1BB and OX40 dual costimulation synergistically stimulate primary specific CD8 T cells for robust effector function
    Seung Joo Lee
    Division of Immunology, University of Connecticut Health Center, Farmington 06032, USA
    J Immunol 173:3002-12. 2004
    ....
  85. ncbi Cross-linking of 4-1BB activates TCR-signaling pathways in CD8+ T lymphocytes
    Kyung Ok Nam
    Immunomodulation Research Center and Graduate Program in Immunology and Biomedicine, University of Ulsan, Ulsan, Korea
    J Immunol 174:1898-905. 2005
    ..These findings demonstrate that 4-1BB is a T cell costimulatory receptor that activates TCR-signaling pathways in CD8+ T cells...
  86. pmc CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB x NZW F1 mice
    Juergen Foell
    Department of Surgery and Emory Vaccine Center, School of Medicine, School of Public Health, Emory University, Atlanta, Georgia, USA
    J Clin Invest 111:1505-18. 2003
    ..In this report we show that lupus-prone NZB x NZW F(1) mice given three injections of anti-CD137 (4-1BB) mAb's between 26 and 35 weeks of age reversed acute disease, blocked chronic disease, and extended the ..
  87. pmc 4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae
    Zheng Qi Wu
    Department of Pathology Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
    Infect Immun 71:196-204. 2003
    4-1BB (CD137) is induced on activated CD4(+) and CD8(+) T cells and delivers a costimulatory signal upon binding the 4-1BB ligand (4-1BBL) expressed on antigen-presenting cells...
  88. ncbi CD137 signaling interferes with activation and function of CD4+CD25+ regulatory T cells in induced tolerance to experimental autoimmune thyroiditis
    Gerald P Morris
    Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA
    Cell Immunol 226:20-9. 2003
    ..Importantly, administration of an agonistic CD137 monoclonal antibody (mAb) inhibited tolerance development, and the mediation of established tolerance...
  89. ncbi Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region
    Junichiro Irie
    Division of Rheumatology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Immunogenetics 58:9-14. 2006
    ..The NOD and B10 CD137 alleles have sequence polymorphisms and different functional effects on T cells; the NOD CD137 allele mediates ..
  90. ncbi Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells
    Toshiro Futagawa
    Department of Immunology, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    Int Immunol 14:275-86. 2002
    4-1BB (CDw137) and its ligand (4-1BBL) have been implicated in cellular immune responses...
  91. ncbi Engagement of 4-1BB inhibits the development of experimental allergic conjunctivitis in mice
    Atsuki Fukushima
    Department of Ophthalmology, Kochi Medical School, Nankoku City, Japan
    J Immunol 175:4897-903. 2005
    ....
  92. ncbi Genetic contributions of nonautoimmune SWR mice toward lupus nephritis
    S Xie
    Simmon s Arthritis Research Center and Center for Immunology, University of Texas Southwestern Medical School, Dallas, TX 75390, USA
    J Immunol 167:7141-9. 2001
    ..In conclusion, lupus in the SNF(1) strain is truly polygenic, with at least four dominant contributions from the SWR strain. The immunological functions and molecular identities of these loci await elucidation...
  93. ncbi Host T cells resist graft-versus-host disease mediated by donor leukocyte infusions
    B R Blazar
    University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis, MN 55455, USA
    J Immunol 165:4901-9. 2000
    ..These same mechanisms may limit the efficacy of DLI in cancer therapy under some conditions...
  94. ncbi Absence of 4 1BB gene function exacerbates lacrimal gland inflammation in autoimmune-prone MRL-Faslpr mice
    Dass S Vinay
    LSU Eye Center, LSU Health Sciences Center School of Medicine, New Orleans, Louisiana, USA
    Invest Ophthalmol Vis Sci 48:4608-15. 2007
    ..To define the role of endogenous 4-1BB (an important T-cell costimulatory molecule) in the regulation of ocular disease, MRL-Fas(lpr) mice deficient in 4-1BB were generated, and their lacrimal gland function was studied...
  95. ncbi The NOD Idd9 genetic interval influences the pathogenicity of insulitis and contains molecular variants of Cd30, Tnfr2, and Cd137
    P A Lyons
    The Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge University, United Kingdom
    Immunity 13:107-15. 2000
    ..Candidate genes with amino acid differences between the NOD and B10 strains have been localized to the 5.6 cM Idd9.2 interval (Tnfr2, Cd30) and to the 2.0 cM Idd9.3 interval (Cd137).
  96. pmc Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel form of 4-1BB ligand eradicates established tumors
    Rajesh K Sharma
    Institute for Cellular Therapeutics, Department of Microbiology and Immunology, and James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
    Cancer Res 69:4319-26. 2009
    ..Potent pleiotropic immunomodulatory activities combined with lack of toxicity highlight the potential of 4-1BBL molecule as an effective component of therapeutic cancer vaccines...
  97. ncbi Contribution of CD30/CD153 but not of CD27/CD70, CD134/OX40L, or CD137/4-1BBL to the optimal induction of protective immunity to Mycobacterium avium
    Manuela Flórido
    Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, Portugal
    J Leukoc Biol 76:1039-46. 2004
    A panel of monoclonal antibodies specific for CD27 ligand (CD70), CD30 ligand (CD153), CD134 ligand (OX40L), and CD137 ligand (4-1BBL) were screened in vivo for their ability to affect the control of Mycobacterium avium infection in ..
  98. ncbi Analysis of expression and function of the costimulatory molecule 4-1BB in alloimmune responses
    J T Tan
    The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA
    Transplantation 70:175-83. 2000
    4-1BB (CD137) is a T cell costimulatory molecule that promotes T cell activation. In this study, we investigated the role of 4-1BB costimulation in allogeneic T cell responses.