Arlene H Sharpe

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection
    Arlene H Sharpe
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nat Immunol 8:239-45. 2007
  2. pmc Tissue expression of PD-L1 mediates peripheral T cell tolerance
    Mary E Keir
    Department of Pathology, Brigham and Women s Hospital and Children s Hospital Boston, MA 02115, USA
    J Exp Med 203:883-95. 2006
  3. ncbi request reprint CD70 signaling is critical for CD28-independent CD8+ T cell-mediated alloimmune responses in vivo
    Akira Yamada
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 174:1357-64. 2005
  4. ncbi request reprint Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart
    Nir Grabie
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Circulation 116:2062-71. 2007
  5. pmc Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice
    Julie A Lucas
    Laboratory of Molecular Autoimmune Disease, Renal Division, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 181:2513-21. 2008
  6. pmc Programmed death-1 (PD-1):PD-ligand 1 interactions inhibit TCR-mediated positive selection of thymocytes
    Mary E Keir
    Department of Pathology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115 5727, USA
    J Immunol 175:7372-9. 2005
  7. pmc Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade
    Erika D Reynoso
    Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 182:2102-12. 2009
  8. pmc PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells
    Yvette E Latchman
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:10691-6. 2004
  9. ncbi request reprint PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis
    Spencer C Liang
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Eur J Immunol 36:58-64. 2006
  10. pmc The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells
    Aurelie T Bauquet
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 10:167-75. 2009

Detail Information

Publications93

  1. ncbi request reprint The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection
    Arlene H Sharpe
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nat Immunol 8:239-45. 2007
    ..Here we examine the functions of PD-1 and its ligands in regulating antimicrobial and self-reactive T cell responses and discuss the therapeutic potential of manipulating this pathway...
  2. pmc Tissue expression of PD-L1 mediates peripheral T cell tolerance
    Mary E Keir
    Department of Pathology, Brigham and Women s Hospital and Children s Hospital Boston, MA 02115, USA
    J Exp Med 203:883-95. 2006
    ..These data provide evidence that PD-L1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1-PD-L1 interactions in mediating tissue tolerance...
  3. ncbi request reprint CD70 signaling is critical for CD28-independent CD8+ T cell-mediated alloimmune responses in vivo
    Akira Yamada
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 174:1357-64. 2005
    ..These novel findings have important implications for the development of transplantation tolerance-inducing strategies in primates and humans, in which CD8(+) T cell depletion is currently mandatory...
  4. ncbi request reprint Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart
    Nir Grabie
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Circulation 116:2062-71. 2007
    ..PD-L1 is induced on cardiac endothelial cells under inflammatory conditions, but little is known about its role in regulating immune injury in the heart...
  5. pmc Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice
    Julie A Lucas
    Laboratory of Molecular Autoimmune Disease, Renal Division, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 181:2513-21. 2008
    ..Taken together, we suggest that PD-L1 expression is central to autoimmune heart and lung disease in lupus-susceptible (MRL) mice...
  6. pmc Programmed death-1 (PD-1):PD-ligand 1 interactions inhibit TCR-mediated positive selection of thymocytes
    Mary E Keir
    Department of Pathology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115 5727, USA
    J Immunol 175:7372-9. 2005
    ..These data demonstrate that PD-1:PD-L1 interactions are critical to positive selection and play a role in shaping the T cell repertoire...
  7. pmc Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade
    Erika D Reynoso
    Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 182:2102-12. 2009
    ..Collectively, these results indicate that loss of the PD-1:PD-L1 inhibitory pathway breaks CD8(+) T cell tolerance to intestinal self-Ag, thus leading to severe enteric autoimmunity...
  8. pmc PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells
    Yvette E Latchman
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:10691-6. 2004
    ..These results demonstrate that PD-L1 on T cells, APCs, and host tissue inhibits naïve and effector T cell responses and plays a critical role in T cell tolerance...
  9. ncbi request reprint PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis
    Spencer C Liang
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Eur J Immunol 36:58-64. 2006
    ..Taken together, our results demonstrate that PD-L1 and PD-L2 have distinct roles in regulating the immune response to L. mexicana...
  10. pmc The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells
    Aurelie T Bauquet
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 10:167-75. 2009
    ..Genetic loss of c-Maf resulted in a defect in IL-21 production and fewer T(H)-17 and T(FH) cells. Thus our data suggest that ICOS-induced c-Maf regulates IL-21 production that in turn regulates the expansion of T(H)-17 and T(FH) cells...
  11. pmc The programmed death-1 ligand 1:B7-1 pathway restrains diabetogenic effector T cells in vivo
    Alison M Paterson
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 187:1097-105. 2011
    ....
  12. pmc Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation
    De xiu Bu
    Department of Pathology, Brigham and Women s Hospital, and Department of Medicine, Harvard Medical School, NRB Rm 752N, 77 Ave Louis Pasteur, Boston, MA 02115, USA
    Arterioscler Thromb Vasc Biol 31:1100-7. 2011
    ..We studied the contribution of the PD-1 pathway to regulation of T cells that promote atherosclerotic lesion formation and inflammation...
  13. ncbi request reprint The function of donor versus recipient programmed death-ligand 1 in corneal allograft survival
    Linling Shen
    Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 179:3672-9. 2007
    ....
  14. ncbi request reprint Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses
    Spencer C Liang
    Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA
    Eur J Immunol 33:2706-16. 2003
    ..PD-L2, but not PD-L1, expression was dramatically reduced in p50(-/-)p65(+/-) DC. Thus, PD-L1 and PD-L2 exhibit distinct expression patterns and are differentially regulated on the transcriptional level...
  15. doi request reprint Regulation of T-cell chemotaxis by programmed death-ligand 1 (PD-L1) in dry eye-associated corneal inflammation
    Jaafar El Annan
    Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
    Invest Ophthalmol Vis Sci 51:3418-23. 2010
    ..Downregulation of corneal epithelial PD-L1 amplifies dry eye-associated corneal inflammation and epitheliopathy by increasing the expression of chemokine ligands and receptors that promote T-cell homing to the ocular surface...
  16. ncbi request reprint PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues
    Mary E Keir
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 179:5064-70. 2007
    ....
  17. ncbi request reprint Programmed death 1 ligand (PD-L) 1 and PD-L2 limit autoimmune kidney disease: distinct roles
    Julia Menke
    Laboratory of Molecular Autoimmune Disease, Renal Division, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 179:7466-77. 2007
    ..Taken together, our findings indicate that PD-L1 and PD-L2 provide distinct negative regulatory checkpoints poised to suppress autoimmune renal disease...
  18. pmc ICOS/ICOSL interaction is required for CD4+ invariant NKT cell function and homeostatic survival
    Omid Akbari
    Division of Immunology, Children s Hospital, Harvard Medical School, Boston, MA, 02115, USA
    J Immunol 180:5448-56. 2008
    ..These results indicate that ICOS costimulation plays a major role in induction of AHR by iNKT cells and is required for CD4(+) iNKT cell function, homeostasis, and survival in the periphery...
  19. pmc The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo
    Jun Yang
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 187:1113-9. 2011
    ..1 interaction with T cell PDL1 did not. These data indicate that PDL1 interaction with B7.1 plays an important role in the inhibition of alloimmune responses in vivo and suggests a dominant direction for PDL1 and B7.1 interaction...
  20. ncbi request reprint A role for the B7-1/B7-2:CD28/CTLA-4 pathway during negative selection
    Janet E Buhlmann
    Department of Pathology, Immunology Research Division, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 170:5421-8. 2003
    ..Finally, CTLA-4 delivers signals that inhibit selection, suggesting that CTLA-4 and CD28 have opposing functions in thymic development. Combined, the data demonstrate that B7-1/B7-2-dependent signals help shape the T cell repertoire...
  21. pmc Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses
    Manish J Butte
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Immunity 27:111-22. 2007
    ..Our findings point to a substantial bidirectional inhibitory interaction between B7-1 and PD-L1 and add an additional dimension to immunoregulatory functions of the B7:CD28 family...
  22. pmc Interaction of human PD-L1 and B7-1
    Manish J Butte
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Mol Immunol 45:3567-72. 2008
    ..We show that PD-L1 is induced to a higher level on CD28high T cells than on CD28low T cells upon activation. These results suggest that PD-L1 may play an important and undervalued role on human T cells...
  23. pmc Overexpression of the Ctla-4 isoform lacking exons 2 and 3 causes autoimmunity
    Sue M Liu
    Center for Neurologic Diseases, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 188:155-62. 2012
    ..Collectively, these data suggest that the function of the 1/4CTLA-4 isoform is distinct from that of CTLA-4 in that it enhances T cell activation and promotes autoimmunity rather than inhibiting immune responses...
  24. ncbi request reprint Role of the B7-CD28/CTLA-4 pathway in autoimmune disease
    Tammy T Chang
    Immunology Research Division, Department of Pathology, Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Mass, USA
    Curr Dir Autoimmun 5:113-30. 2002
  25. ncbi request reprint Genetic background determines the requirement for B7 costimulation in induction of autoimmunity
    Claudia Jabs
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Eur J Immunol 32:2687-97. 2002
    ..Thus, genetic background determines the B7 requirement for inducing autoimmunity. These data have important implications for developing B7-based immunotherapies for human diseases...
  26. pmc PD-L1 regulates the development, maintenance, and function of induced regulatory T cells
    Loise M Francisco
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 206:3015-29. 2009
    ..These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity...
  27. ncbi request reprint Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity
    K Mark Ansel
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 5:1251-9. 2004
    ....
  28. ncbi request reprint B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice
    Chiara Buono
    Immunology Research Division and the Vascular Research Division, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Mass 02115, USA
    Circulation 109:2009-15. 2004
    ..This study tested the hypothesis that the ability of T cells to influence atherosclerosis depends on B7-1/B7-2 costimulation...
  29. pmc A novel function for programmed death ligand-1 regulation of angiogenesis
    Yiping Jin
    Department of Ophthalmology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA
    Am J Pathol 178:1922-9. 2011
    ..We conclude that the expression of PD-L1 in both vascular endothelial cells and corneal epithelial cells regulates corneal angiogenesis...
  30. ncbi request reprint The B7 family revisited
    Rebecca J Greenwald
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Annu Rev Immunol 23:515-48. 2005
    ..In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential...
  31. pmc Role of PD-1 in regulating acute infections
    Keturah E Brown
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Curr Opin Immunol 22:397-401. 2010
    ..Thus, PD-1 can influence adaptive immune responses during acute infections, though precisely how this regulation occurs is only just beginning to be appreciated...
  32. ncbi request reprint Cutting edge: CTLA-4 (CD152) differentially regulates mitogen-activated protein kinases (extracellular signal-regulated kinase and c-Jun N-terminal kinase) in CD4+ T cells from receptor/ligand-deficient mice
    Helga Schneider
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Immunol 169:3475-9. 2002
    ..Our findings demonstrate that CTLA-4 cosignaling is more complex than previously appreciated, with an ability to differentially regulate members of the MAPK family in T cells...
  33. ncbi request reprint The ICOS molecule plays a crucial role in the development of mucosal tolerance
    Katsuichi Miyamoto
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 175:7341-7. 2005
    ..These results suggest that stimulating ICOS may provide an effective therapeutic approach for promoting mucosal tolerance...
  34. ncbi request reprint The B7-CD28 superfamily
    Arlene H Sharpe
    Immunology Research Division, Department of Pathology, Brigham, and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Rev Immunol 2:116-26. 2002
    ..Here, we summarize our current understanding of the new members of the B7 and CD28 families, and discuss their therapeutic potential...
  35. ncbi request reprint Negative co-receptors on lymphocytes
    Rebecca J Greenwald
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, 221 Longwood Avenue, Boston, MA 02115, USA
    Curr Opin Immunol 14:391-6. 2002
    ..Recent studies indicate that ICOS exerts distinct effects at different phases of an immune response: ICOS can inhibit as well as stimulate T cell responses...
  36. pmc Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade
    Gordon J Freeman
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 203:2223-7. 2006
    ..New studies now extend these observations to HIV infection and human disease...
  37. pmc The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity
    Hiroshi Harada
    Department of Medicine, Children s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 112:234-43. 2003
    ..These data define the complex functions of the ICOS-B7h pathway in regulating alloimmune responses in vivo...
  38. pmc Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions
    Kyung Mi Lee
    Department of Pathology, University of Chicago, IL, USA
    Blood 107:3181-8. 2006
    ..Thus, these data identify a novel mechanism whereby NK effector function is regulated via homotypic 2B4/CD48 interactions...
  39. pmc Antigen recognition is facilitated by invadosome-like protrusions formed by memory/effector T cells
    Peter T Sage
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 188:3686-99. 2012
    ..Together, our results indicate that ILPs function as sensory organelles that serve as actuators of immune surveillance...
  40. pmc The PD-1 pathway in tolerance and autoimmunity
    Loise M Francisco
    Department of Pathology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    Immunol Rev 236:219-42. 2010
    ..Thus, this review also discusses how the PD-1 pathway regulates a number of autoimmune diseases and the therapeutic potential of PD-1: PD-L modulation...
  41. pmc Auto-antibody production and glomerulonephritis in congenic Slamf1-/- and Slamf2-/- [B6.129] but not in Slamf1-/- and Slamf2-/- [BALB/c.129] mice
    Marton Keszei
    Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Int Immunol 23:149-58. 2011
    ..Functional analyses of CD4(+) T cells reveals that Slamf2(-/-) T cells are resistant to tolerance induction in vivo. We conclude that the Slamf2(-/-) mutation may have a unique influence on T-cell tolerance and lupus...
  42. ncbi request reprint Rap1-GTP is a negative regulator of Th cell function and promotes the generation of CD4+CD103+ regulatory T cells in vivo
    Lequn Li
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 175:3133-9. 2005
    ....
  43. pmc Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice
    Manabu Araki
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Center for Neurologic Diseases, Boston, MA 02115, USA
    J Immunol 183:5146-57. 2009
    ..These results suggest that liCTLA-4 can partially replace some functions of flCTLA-4 in vivo and that this isoform evolved to reinforce the function of flCTLA-4...
  44. ncbi request reprint The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens
    Jens Lohr
    Department of Pathology, University of California San Francisco School of Medicine, San Francisco, California 94143 0511, USA
    Nat Immunol 4:664-9. 2003
    ..Thus, constitutively expressed B7 costimulators function to suppress T cell activation and maintain self-tolerance, principally by sustaining a population of regulatory T cells...
  45. doi request reprint PD-1 and its ligands in tolerance and immunity
    Mary E Keir
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115 5727, USA
    Annu Rev Immunol 26:677-704. 2008
    ..In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential...
  46. pmc B7h (ICOS-L) maintains tolerance at the fetomaternal interface
    Leonardo V Riella
    Transplantation Research Center, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Am J Pathol 182:2204-13. 2013
    ..Taken together, these data support the hypothesis that B7h blockade abrogates tolerance at the fetomaternal interface by enhancing CD8(+) effector response and reducing local immunomodulation mediated by CD8(+) regulatory T cells...
  47. ncbi request reprint Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis
    Nancy Rodig
    The Immunology Research Division, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Eur J Immunol 33:3117-26. 2003
    ..Our findings highlight a potentially important pathway by which endothelial cells down-regulate CD8+ T cell-mediated immune responses...
  48. pmc The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood
    Peter T Sage
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Immunol 14:152-61. 2013
    ..Our findings demonstrate mechanisms by which the PD-1 pathway regulates antibody production and help reconcile inconsistencies surrounding the role of this pathway in humoral immunity...
  49. pmc PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis
    Margarite L Tarrio
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 188:4876-84. 2012
    ..Together, these studies show that PD-1 plays an important role in limiting T cell responses in the heart...
  50. pmc The cell surface receptor SLAM controls T cell and macrophage functions
    Ninghai Wang
    Division of Immunology, RE 204, Beth Israel Deaconess Medical Center, Harvard Medical School, 41 Avenue Louis Pasteur, Boston, MA 02215, USA
    J Exp Med 199:1255-64. 2004
    ..We conclude that the coreceptor SLAM plays a central role at the interface of acquired and innate immune responses...
  51. ncbi request reprint T-cell costimulation--biology, therapeutic potential, and challenges
    Arlene H Sharpe
    Harvard Medical School, Boston, USA
    N Engl J Med 355:973-5. 2006
  52. ncbi request reprint T helper differentiation in resistant and susceptible B7-deficient mice infected with Leishmania major
    Julia A Brown
    Department of Pathology, Immunology Research Division, Brigham and Women s Hospital, Boston, MA, USA
    Eur J Immunol 32:1764-72. 2002
    ..major, whereas BALB/c B7-1-deficient mice remain as susceptible as wild-type BALB/c mice. Differential expression of B7-1 and B7-2 can explain the distinct roles observed for these B7 costimulators in L. major infection...
  53. pmc TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells
    Norimoto Kobayashi
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Harvard Medical School, Boston, MA 02115, USA
    Immunity 27:927-40. 2007
    ..These results show that TIM-4 and TIM-1 are immunologically restricted members of the group of receptors whose recognition of PS is critical for the efficient clearance of apoptotic cells and prevention of autoimmunity...
  54. ncbi request reprint The threshold pattern of calcineurin-dependent gene expression is altered by loss of the endogenous inhibitor calcipressin
    Sandra Ryeom
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Immunol 4:874-81. 2003
    ..Thus, calcipressins modulate the pattern of calcineurin-dependent transcription, and may influence calcineurin activity beyond calcium to integrate a broad array of signals into the cellular response...
  55. ncbi request reprint PD-1 and its ligands in T-cell immunity
    Mary E Keir
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Curr Opin Immunol 19:309-14. 2007
    ..Finally, PD-1 has recently been shown to be highly expressed on exhausted T cells during chronic viral infection, and blockade of PD-1 or PD-L1 can revive exhausted T cells, enabling them to proliferate and produce effector cytokines...
  56. pmc Cutting edge: an NK cell-independent role for Slamf4 in controlling humoral autoimmunity
    Daniel R Brown
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 187:21-5. 2011
    ..Taken together, our findings reveal that slamf4 has an NK cell-independent negative regulatory role in the pathogenesis of lupus a normally non-autoimmune prone genetic background...
  57. ncbi request reprint Recovery from EAE is associated with decreased survival of encephalitogenic T cells in the CNS of B7-1/B7-2-deficient mice
    Tammy T Chang
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA
    Eur J Immunol 33:2022-2032. 2003
    ....
  58. pmc Circulatory antigen processing by mucosal dendritic cells controls CD8(+) T cell activation
    Sun Young Chang
    Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Immunity 38:153-65. 2013
    ....
  59. ncbi request reprint Impaired regulatory T-cell response and enhanced atherosclerosis in the absence of inducible costimulatory molecule
    Israel Gotsman
    Immunology Division, Brigham and Women s Hospital, and Harvard Medical School, Boston, Mass 02115, USA
    Circulation 114:2047-55. 2006
    ..We explored the influence of the inducible costimulatory molecule (ICOS) on atherosclerosis and associated immune responses...
  60. pmc Intrafollicular location of marginal zone/CD1d(hi) B cells is associated with autoimmune pathology in a mouse model of lupus
    Biyan Duan
    Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610 0275, USA
    Lab Invest 88:1008-20. 2008
    ..These results suggest that follicular exclusion of IgM+ CD1d(hi)/MZ B cells is an important B-cell tolerance mechanism, and that B7-2 signaling is involved in breaching this tolerance checkpoint...
  61. pmc Brief report: increased expression of a short splice variant of CTLA-4 exacerbates lupus in MRL/lpr mice
    Kunihiro Ichinose
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Arthritis Rheum 65:764-9. 2013
    ..This study was undertaken to evaluate the role of the 1/4 CTLA-4 isoform in lupus-prone mice...
  62. ncbi request reprint The B7/CD28 costimulatory family in autoimmunity
    Mary E Keir
    Department of Pathology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115 5727, USA
    Immunol Rev 204:128-43. 2005
    ..We also discuss how B7/CD28 pathways influence both T-cell-intrinsic and -extrinsic mechanisms of regulation...
  63. pmc Anti-CD3 mAb treatment cures PDL1-/-.NOD mice of diabetes but precipitates fatal myocarditis
    Bechara Mfarrej
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Clin Immunol 140:47-53. 2011
    ..NOD mice as the mice develop T1D at an early age and die from diabetes prior to manifesting other autoimmune diseases...
  64. ncbi request reprint Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation
    Ruth S S Arestides
    Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Eur J Immunol 32:2874-80. 2002
    ..Levels of allergen-induced Th1 as well as Th2 cytokines were also significantly reduced. Together, the data support a critical role for OX40L signals in allergic responses...
  65. ncbi request reprint Inducible co-stimulator null MRL-Faslpr mice: uncoupling of autoantibodies and T cell responses in lupus
    Geraldine C Zeller
    Laboratory of Molecular Autoimmune Disease, Renal Divison, Brigham and Womens Hospital, Boston, MA 02115, USA
    J Am Soc Nephrol 17:122-30. 2006
    ..These findings highlight the danger of relying on individual parameters, such as quantitative serum Ig levels and T cell functions, as prognostic indicators of lupus...
  66. pmc Modulation of surgical fibrosis by microbial zwitterionic polysaccharides
    Begonia Ruiz-Perez
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:16753-8. 2005
    ....
  67. pmc Cutting edge: TIGIT has T cell-intrinsic inhibitory functions
    Nicole Joller
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 186:1338-42. 2011
    ..Microarray analysis of T cells stimulated with agonistic anti-TIGIT Ab revealed that TIGIT can act directly on T cells by attenuating TCR-driven activation signals...
  68. pmc The SLAM family member CD48 (Slamf2) protects lupus-prone mice from autoimmune nephritis
    Anna E Koh
    Division of Pediatric Nephrology, Harvard Medical School and Massachusetts General Hospital, Boston, 02114, USA
    J Autoimmun 37:48-57. 2011
    ..129CD48(-/-) animals, neither BALB.129CD48(-/-) mice nor B6 × BALB/c F1.129CD48(-/-) progeny have autoimmune traits, indicating that B6-specific background genes modulate the effect of CD48 on lupus nephritis in a recessive manner...
  69. pmc Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells
    Caroline Pot
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 183:797-801. 2009
    ..ICOS further promotes IL-27-driven Tr1 cells. Each of those elements is essential, because loss of c-Maf, IL-21-signaling, or ICOS decreases the frequency of IL-27-induced differentiation of IL-10-producing Tr1 cells...
  70. ncbi request reprint Cutting edge: inducible costimulator protein regulates both Th1 and Th2 responses to cutaneous leishmaniasis
    Rebecca J Greenwald
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 168:991-5. 2002
    ..mexicana-specific Ig isotype class switching to IgG1 and IgG2a and reduced total IgE levels. Our findings indicate that ICOS is a key regulator of both Th1 and Th2 responses and has a role in controlling cutaneous L. mexicana infection...
  71. ncbi request reprint CTLA-4 regulates cell cycle progression during a primary immune response
    Rebecca J Greenwald
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02215, USA
    Eur J Immunol 32:366-73. 2002
    ..Re-expression of the cell cycle inhibitor p27(kip1) is delayed in the absence of CTLA-4. These studies demonstrate that the B7 : CTLA-4 pathway exerts its major effects on T cell immune responses via regulation of the cell cycle...
  72. ncbi request reprint ICOS contributes to T cell expansion in CTLA-4 deficient mice
    Miranda E A T van Berkel
    Department of Immunology, University Medical Center, Utrecht, The Netherlands
    J Immunol 175:182-8. 2005
    ..These results indicate that ICOS is not only important for T cell effector function but also contributes to the expansion phase of a T cell response in the presence of CD28 signaling...
  73. ncbi request reprint Memory Th2 effector cells can develop in the absence of B7-1/B7-2, CD28 interactions, and effector Th cells after priming with an intestinal nematode parasite
    Melinda J Ekkens
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 168:6344-51. 2002
    ..However, humoral immunity is impaired and differentially affected in B7-1/B7-2(-/-) mice and CD28(-/-) mice following H. polygyrus challenge...
  74. ncbi request reprint Protect the killer: CTLs need defenses against the tumor
    Gordon J Freeman
    Nat Med 8:787-9. 2002
  75. ncbi request reprint CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis
    Antonella Mencacci
    Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia, Italy
    J Immunol 169:3180-90. 2002
    ..These data indicate that alternatively activated PMN expressing CD80 may adversely affect Th1-dependent resistance in fungal infections...
  76. ncbi request reprint Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity
    Omid Akbari
    Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, Stanford University, Stanford, California, USA
    Nat Med 8:1024-32. 2002
    ..These studies demonstrate that T(R) cells and the ICOS-ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma...
  77. ncbi request reprint Cutting edge: a crucial role for B7-CD28 in transmitting T help from APC to CTL
    Kiley R Prilliman
    Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    J Immunol 169:4094-7. 2002
    ..These results support a model in which activation-induced up-regulation of B7 molecules on APC leads to increased CD28 signaling and a commitment to cross-priming of CD4-dependent CTL...
  78. pmc The CD154/CD40 interaction required for retrovirus-induced murine immunodeficiency syndrome is not mediated by upregulation of the CD80/CD86 costimulatory molecules
    Kathy A Green
    Department of Microbiology and Immunology and the Norris Cotton Cancer Center, Dartmouth Medical School, Borwell Building, Lebanon, NH 03756, USA
    J Virol 76:13106-10. 2002
    ..Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86(-/-) B6 mice develop MAIDS after LP-BM5 infection...
  79. ncbi request reprint Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo
    Simon Read
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom
    J Immunol 177:4376-83. 2006
    ..This role has to be taken into account when targeting CTLA-4 for therapeutic purposes, as such a strategy will not only boost effector T cell responses, but might also break T(R)-mediated self-tolerance...
  80. ncbi request reprint Analysis of the role of negative T cell costimulatory pathways in CD4 and CD8 T cell-mediated alloimmune responses in vivo
    Toshiro Ito
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, MA 02115, USA
    J Immunol 174:6648-56. 2005
    ..Harnessing physiological mechanisms that regulate alloimmunity should lead to development of novel strategies to induce durable and reproducible transplantation tolerance...
  81. ncbi request reprint An important role of CD80/CD86-CTLA-4 signaling during photocarcinogenesis in mice
    Karin Loser
    Department of Dermatology, University of Munster, Munster, Germany
    J Immunol 174:5298-305. 2005
    ..Furthermore, CD86-mediated costimulation appears to play a more critical role in the protection against photocarcinogenesis than CD80...
  82. pmc Induction of autoimmune disease in CTLA-4-/- mice depends on a specific CD28 motif that is required for in vivo costimulation
    Xuguang Tai
    Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 104:13756-61. 2007
    ....
  83. pmc Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection
    Scott N Mueller
    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 104:15430-5. 2007
    ..These data also suggest that the inhibitory PD-1 pathway, which likely evolved to prevent excessive immunopathology, may contribute to viral persistence in FRC during chronic infection...
  84. ncbi request reprint Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM)
    Patricia A Taylor
    University of Minnesota Cancer Center and Department of Pediatrics, Division of BMT, Minneapolis, MN 55455, USA
    Blood 105:3372-80. 2005
    ..These data suggest that the ICOS pathway may be a beneficial therapeutic target for GVHD inhibition, GVHD therapy, and BM graft promotion...
  85. ncbi request reprint 4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses
    Wojciech Dawicki
    Department of Immunology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada
    J Immunol 173:5944-51. 2004
    ..Thus, 4-1BB and OX40 act independently and nonredundantly to facilitate robust CD4 and CD8 recall responses...
  86. ncbi request reprint An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells
    Lalitha Vijayakrishnan
    Center for Neurologic Diseases, Department of Neurology, Boston, MA 02115 USA
    Immunity 20:563-75. 2004
    ..These data suggest that increased expression and negative signaling delivered by the liCTLA-4 may regulate development of T cell-mediated autoimmune diseases...
  87. ncbi request reprint B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via T-T interactions [corrections]
    Patricia A Taylor
    Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, 425 East River Road, Minneapolis, MN 55455, USA
    J Immunol 172:34-9. 2004
    ..The up-regulation of B7 on T cells may be an important component of normal immune homeostasis...
  88. pmc Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection
    Sang Jun Ha
    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Exp Med 205:543-55. 2008
    ..Such an approach may have broad applications in developing treatment strategies for chronic infections in general, and perhaps also for tumors...
  89. ncbi request reprint Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogeneic bone marrow transplant recipients
    Bruce R Blazar
    University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis, MN, USA
    Blood 101:3741-8. 2003
    ..These data provide insights as to the mechanisms responsible for OX40/OX40L regulation of GVHD...
  90. ncbi request reprint The role of OX40 ligand interactions in the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus
    Melinda J Ekkens
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 170:384-93. 2003
    ..polygyrus. However, OX40L interactions were not required for serum IgG1 elevations, increases in germinal center formation, and Ag-specific Th2 cell expansion and migration to the B cell zone...
  91. ncbi request reprint Nippostrongylus brasiliensis can induce B7-independent antigen-specific development of IL-4-producing T cells from naive CD4 T cells in vivo
    Zhugong Liu
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 169:6959-68. 2002
    ..10 Th2 cell differentiation; however, DO11.10 T cell cycle progression and migration to the B cell zone are inhibited...
  92. ncbi request reprint B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans
    Claudia Montagnoli
    Microbiology Section, Department of Experimental Medicine and Biochemical Science, University of Perugia, Italy
    J Immunol 169:6298-308. 2002
    ..The implication is that preventing reactivation rather than favoring sterilizing immunity to ubiquitous fungal pathogens may represent the ultimate expectation of vaccine-based strategies...
  93. ncbi request reprint Restoring function in exhausted CD8 T cells during chronic viral infection
    Daniel L Barber
    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Nature 439:682-7. 2006
    ..These studies identify a specific mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections...