M Exley

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24 J alpha Q T cell receptor alpha chains
    M Exley
    Department of Cancer Biology, Hematology Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Exp Med 188:867-76. 1998
  2. pmc Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loop
    Mark A Exley
    Hematology Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Eur J Immunol 38:1756-66. 2008
  3. pmc Developing understanding of the roles of CD1d-restricted T cell subsets in cancer: reversing tumor-induced defects
    Mark A Exley
    Department of Medicine, Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Clin Immunol 140:184-95. 2011
  4. ncbi To be or not to be NKT: natural killer T cells in the liver
    Mark A Exley
    Division of Hematology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Hepatology 40:1033-40. 2004
  5. ncbi Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liver
    Mark A Exley
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Immunol 168:1519-23. 2002
  6. ncbi NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance
    K H Sonoda
    Schepens Eye Research Institute, Harvard Medical School, Boston MA 02114, USA
    J Immunol 166:42-50. 2001
  7. ncbi Characterization of the phenotype and function of CD8(+), alpha / beta(+) NKT cells from tumor-bearing mice that show a natural killer cell activity and lyse multiple tumor targets
    C Stremmel
    Center for Neurological Diseases, Brigham and Womens Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Eur J Immunol 31:2818-28. 2001
  8. ncbi Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice
    L J Saubermann
    Division of Gastroenterology and the Harvard Digestive Diseases Center, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Gastroenterology 119:119-28. 2000
  9. pmc CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo
    Petr O Ilyinskii
    Cancer Biology Program, Hematology Oncology Division, Beth Israel Deaconess Medical Center, NRB 1030L, 330 Brookline Avenue, Boston, MA 02215, USA
    J Virol 80:7146-58. 2006
  10. pmc Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo
    Simon C Yue
    Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    J Immunol 184:268-76. 2010

Collaborators

Detail Information

Publications38

  1. pmc CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24 J alpha Q T cell receptor alpha chains
    M Exley
    Department of Cancer Biology, Hematology Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Exp Med 188:867-76. 1998
    ..These results demonstrate a role for CD161 as a novel costimulatory molecule for TCR-mediated recognition of CD1d by human V alpha 24(invt) T cells...
  2. pmc Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loop
    Mark A Exley
    Hematology Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Eur J Immunol 38:1756-66. 2008
    ..Specifically, an anti-Valpha24Jalpha18 CDR3 loop clonotypic TCR mAb is available for the enumeration and therapeutic manipulation of human and non-human primate iNKT populations...
  3. pmc Developing understanding of the roles of CD1d-restricted T cell subsets in cancer: reversing tumor-induced defects
    Mark A Exley
    Department of Medicine, Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Clin Immunol 140:184-95. 2011
    ....
  4. ncbi To be or not to be NKT: natural killer T cells in the liver
    Mark A Exley
    Division of Hematology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Hepatology 40:1033-40. 2004
    ..Although there is an abundance of literature on the phenotype, distribution, and function of these cells in mice, much less is known about them in human health or liver diseases...
  5. ncbi Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liver
    Mark A Exley
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Immunol 168:1519-23. 2002
    ..These results identify a novel population of human T cells that could contribute to destructive as well as protective immune responses in the liver. CD1d-reactive T cells may have distinct roles in different tissues...
  6. ncbi NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance
    K H Sonoda
    Schepens Eye Research Institute, Harvard Medical School, Boston MA 02114, USA
    J Immunol 166:42-50. 2001
    ..Thus, NK T cell-derived IL-10 is critical for the generation of the Ag-specific Tr cells and systemic tolerance induced to eye-inoculated Ags...
  7. ncbi Characterization of the phenotype and function of CD8(+), alpha / beta(+) NKT cells from tumor-bearing mice that show a natural killer cell activity and lyse multiple tumor targets
    C Stremmel
    Center for Neurological Diseases, Brigham and Womens Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Eur J Immunol 31:2818-28. 2001
    ..CD161(+) T cells that are expanded in tumor-bearing hosts may function as a part of the innate immune system with potential role(s) in tumor surveillance...
  8. ncbi Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice
    L J Saubermann
    Division of Gastroenterology and the Harvard Digestive Diseases Center, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Gastroenterology 119:119-28. 2000
    ..1(+) T cells. These NK T cells exhibit important immunoregulatory functions in several autoimmune disease models...
  9. pmc CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo
    Petr O Ilyinskii
    Cancer Biology Program, Hematology Oncology Division, Beth Israel Deaconess Medical Center, NRB 1030L, 330 Brookline Avenue, Boston, MA 02215, USA
    J Virol 80:7146-58. 2006
    ..These results point to the existence of a previously unrecognized mechanism of rapid CD1d-dependent stimulation of the antiviral adaptive cellular immune response...
  10. pmc Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo
    Simon C Yue
    Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    J Immunol 184:268-76. 2010
    ..These data indicate that NKT cells can be bypassed with CD1d-mediated induction of robust Th1 immunity, which may have therapeutic potential both directly and as an adjuvant...
  11. ncbi Hepatic CD1d expression in hepatitis C virus infection and recognition by resident proinflammatory CD1d-reactive T cells
    Emanuele Durante-Mangoni
    Infectious Diseases Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 173:2159-66. 2004
    ..This process may be beneficial in acute viral clearance, but in chronic infection could contribute to liver injury...
  12. pmc Circulating myeloid dendritic cells of advanced cancer patients result in reduced activation and a biased cytokine profile in invariant NKT cells
    Hans J J van der Vliet
    Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 180:7287-93. 2008
    ....
  13. pmc Defective NKT cell activation by CD1d+ TRAMP prostate tumor cells is corrected by interleukin-12 with α-galactosylceramide
    Michael Nowak
    Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e11311. 2010
    ..These data underscore the potential to optimize iNKT-based therapeutic approaches...
  14. pmc CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes
    M Exley
    Cancer Biology Program, Hematology Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Immunology 100:37-47. 2000
    ..These results demonstrate constitutive CD1d expression by human professional antigen-presenting cells and that post-translational processing of CD1d may contribute to regulation of the activity of CD1d-specific T cells...
  15. pmc CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site
    K H Sonoda
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Exp Med 190:1215-26. 1999
    ..A critical role for NKT cells in the development of systemic tolerance associated with an immune-privileged site suggests a mechanism involving NKT cells in self-tolerance and their defects in autoimmunity...
  16. ncbi CD1d and CD1d-restricted iNKT-cells play a pivotal role in contact hypersensitivity
    Edward E S Nieuwenhuis
    Gastrointestinal Division, Brigham and Women s Hospital, Boston, MA, USA
    Exp Dermatol 14:250-8. 2005
    ..Thus, pharmacologic antagonists of CD1d can be used as effective inhibitors of CHS, a prototype for a variety of delayed-type tissue hypersensitivity responses...
  17. pmc Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor beta that can suppress HCV-specific T-cell responses
    Nadia Alatrakchi
    Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA
    J Virol 81:5882-92. 2007
    ..In conclusion, blockade of TGF-beta secretion could enhance peripheral HCV-specific T-cell responses even in the presence of HIV coinfection...
  18. pmc CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion
    Silke Gillessen
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:8874-9. 2003
    ..DCs from immunized CD1d-deficient mice showed compromised maturation and function. Together, these results delineate a role for CD1d-restricted T cell-DC cross talk in the shaping of antitumor immunity...
  19. pmc Innate immune response to encephalomyocarditis virus infection mediated by CD1d
    Mark A Exley
    Cancer Biology Program, Hematology Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Immunology 110:519-26. 2003
    ..We propose that CD1d-reactive T cells respond to early immune signals and function in the innate immune response to a physiological viral infection by rapidly augmenting APC IL-12 production and activating NK cells...
  20. pmc The A2aR adenosine receptor controls cytokine production in iNKT cells
    Michael Nowak
    Department of Medicine, Divison of Hematology Oncology, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA
    Eur J Immunol 40:682-7. 2010
    ..While A2aR inhibits other lymphocyte populations, A2aR is required for the secretion of IL-4 and IL-10 by iNKT cells. These data suggest adenosine:A2aR-mediated mechanisms can control the cytokine secretion pattern of iNKT cells...
  21. pmc Peripheral blood progenitor cell product contains Th1-biased noninvariant CD1d-reactive natural killer T cells: implications for posttransplant survival
    Angela Shaulov
    Department of Hematology Oncology Beth Israel Deaconess Medical Center, Boston, Mass 02215, USA
    Exp Hematol 36:464-72. 2008
    ..Recent data suggests that NKT might contribute to clinical benefits of PBPC...
  22. ncbi Analysis of the major histocompatibility complex in graft rejection revisited by gene expression profiles
    Kenneth Christopher
    Laboratory of Molecular Immunology, Renal Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Transplantation 78:788-98. 2004
    ..The precise role of major histocompatibility complex (MHC) molecules in graft rejection remains incompletely understood. The important role of foreign peptides in the alloimmune response was recently recognized...
  23. pmc Heterogeneity in phenotype and function of CD8+ and CD4/CD8 double-negative Natural Killer T cell subsets in sooty mangabeys
    Namita Rout
    New England Primate Research Center, Harvard Medical School, Southborough, MA, USA
    J Med Primatol 39:224-34. 2010
    ..To investigate differences in the two NKT cell subsets, we compared the phenotype and function of sooty mangabey CD8(+) and DN NKT cells...
  24. pmc CD1d ligation on human monocytes directly signals rapid NF-kappaB activation and production of bioactive IL-12
    Simon C Yue
    Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 102:11811-6. 2005
    ..These findings demonstrate an innate immune signaling function for CD1d and provide a mechanism for the rapid activation of monocytes and iDCs by CD1d-reactive T cells...
  25. pmc Generation of antitumor invariant natural killer T cell lines in multiple myeloma and promotion of their functions via lenalidomide: a strategy for immunotherapy
    Weihua Song
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute Harvard Medical School, Boston, MA 02115, USA
    Clin Cancer Res 14:6955-62. 2008
    ..Therefore, the development of functional iNKT cells may provide a novel strategy for the immunotherapy in multiple myeloma...
  26. ncbi Exploiting regulatory T-cell populations for the immunotherapy of cancer
    Hans J J van der Vliet
    Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Immunother 30:591-5. 2007
    ..Therapeutic modulation of these regulatory T-cell populations is clinically feasible and will potentially allow the induction of effective antitumor immune responses when combined with currently available immunotherapeutic strategies...
  27. pmc Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function
    Sebastian Zeissig
    Division of Gastroenterology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 120:2889-99. 2010
    ..These data highlight MTP as a unique regulator of human metabolic and immune pathways and reveal that ABL is not only a disorder of lipid metabolism but also an immune disease involving CD1...
  28. doi Isolation and functional use of human NK T cells
    Mark A Exley
    Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Immunol . 2003
    ..Support protocols for secondary stimulations and for rapid expansion of invariant NK T cell clones and functional analysis of these cells are also included...
  29. ncbi Natural killer T cell-based cancer immunotherapy
    Hans J J van der Vliet
    Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Clin Cancer Res 12:5921-3. 2006
  30. ncbi Effects of the administration of high-dose interleukin-2 on immunoregulatory cell subsets in patients with advanced melanoma and renal cell cancer
    Hans J van der Vliet
    Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Clin Cancer Res 13:2100-8. 2007
    ..Although IL-2 is well known as a T-cell growth factor, its potential in vivo effects on human immunoregulatory cell subsets are largely unexplored...
  31. doi Invariant natural killer T cells from rhesus macaque spleen and peripheral blood are phenotypically and functionally distinct populations
    Balgansuren Gansuvd
    Department of Surgery, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA
    J Med Primatol 37:1-11. 2008
    ..Here we characterized rhesus macaque NKT cells ex vivo...
  32. pmc Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals
    Anneliese O Speak
    Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom
    Proc Natl Acad Sci U S A 104:5971-6. 2007
    ..iGb3 is therefore unlikely to be a physiologically relevant iNKT cell-selecting ligand in mouse and humans. A detailed study is now warranted to better understand the nature of iNKT cell-selecting ligand(s) in vivo...
  33. ncbi Hyporesponsiveness to natural killer T-cell ligand alpha-galactosylceramide in cancer-bearing state mediated by CD11b+ Gr-1+ cells producing nitric oxide
    Kazuhiko Yanagisawa
    Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
    Cancer Res 66:11441-6. 2006
    ..These results show a novel feature of NKT cell function in cancer. Furthermore, our data suggest a new strategy to enhance NKT cell-mediated anticancer immune responses by suppressing CD11b(+) Gr-1(+) cell functions...
  34. pmc The CD1d-binding glycolipid alpha-galactosylceramide enhances humoral immunity to T-dependent and T-independent antigen in a CD1d-dependent manner
    Gillian A Lang
    Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03766, USA
    Immunology 119:116-25. 2006
    ..Our data show that NKT cells have multiple effects on the induction of a humoral immune response. We propose that NKT cells could be exploited for the development of novel vaccines where protective antibody is required...
  35. pmc Gestation stage-dependent mechanisms of invariant natural killer T cell-mediated pregnancy loss
    Jonathan E Boyson
    Division of Transplantation Surgery and Immunology, Department of Surgery, University of Vermont College of Medicine, Burlington, VT 05405, USA
    Proc Natl Acad Sci U S A 103:4580-5. 2006
    ..Thus, the stage of gestation defined two distinct mechanisms of pregnancy loss: a perforin-dependent mechanism operating at early gestation and a perforin-independent, cytokine-dominated mechanism operating after midgestation...
  36. ncbi Impaired cell surface expression of human CD1d by the formation of an HIV-1 Nef/CD1d complex
    Sungyoo Cho
    Department of Microbiology and Immunology, Indianapolis, IN 46202, USA
    Virology 337:242-52. 2005
    ..Therefore, one means by which HIV-1 may be able to establish a foothold in an infected individual is by directly interfering with the functional cell surface expression of CD1d...
  37. ncbi Phenotypic and functional characterization of long-term cultured rhesus macaque spleen-derived NKT cells
    Balgansuren Gansuvd
    Department of Surgery, Division of Transplantation Immunobiology, University of Alabama, Birmingham, AL 35294, USA
    J Immunol 171:2904-11. 2003
    ..These cells are semianergic, polarized to a uniquely Th3 > T regulatory-1 regulatory cell phenotype, and have regulatory/suppressive function in vitro...
  38. ncbi CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver
    Tony Kenna
    Education and Research Centre, St Vincent s University Hospital, Elm Park, Dublin 4, Ireland
    Cancer Immunol Immunother 56:563-72. 2007
    ..These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c and CD1d and release inflammatory cytokines are abundant in human liver...

Research Grants7

  1. CD1D REACTIVE T CELLS IN BONE MARROW TRANSPLANTATION
    Mark Exley; Fiscal Year: 2002
    ..These preclinical studies are necessary to evaluate the hypothesis that human CD1d-reactive T cells have the therapeutic potential to selectively suppress acute GvH in the context of conventional BM and PBPC transplants for cancer. ..
  2. Innate-like hepatic CD1d-reative NKT cells:Liver Disease
    Mark Exley; Fiscal Year: 2007
    ..I. on acute HCV infection in chimpanzees, as well as on liver immunology and on 'NKT' cells in general. ..
  3. Innate-like hepatic CD1d-reative NKT cells:Liver Disease
    Mark Exley; Fiscal Year: 2007
    ..I. on acute HCV infection in chimpanzees, as well as on liver immunology and on 'NKT' cells in general. ..