Research Topics
Genomes and Genes | M ExleySummaryAffiliation: Harvard University Country: USA Publications
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Publications
CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24 J alpha Q T cell receptor alpha chainsM 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...- Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loopMark 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... - Developing understanding of the roles of CD1d-restricted T cell subsets in cancer: reversing tumor-induced defectsMark 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.... 
To be or not to be NKT: natural killer T cells in the liverMark 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...- Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liverMark 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... - NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic toleranceK 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... - 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 targetsC 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... - Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in miceL 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... - CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivoPetr 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... - Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivoSimon 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... - Hepatic CD1d expression in hepatitis C virus infection and recognition by resident proinflammatory CD1d-reactive T cellsEmanuele 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... - Circulating myeloid dendritic cells of advanced cancer patients result in reduced activation and a biased cytokine profile in invariant NKT cellsHans 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.... - Defective NKT cell activation by CD1d+ TRAMP prostate tumor cells is corrected by interleukin-12 with α-galactosylceramideMichael 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... - CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytesM 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... - CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged siteK 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... - CD1d and CD1d-restricted iNKT-cells play a pivotal role in contact hypersensitivityEdward 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... - Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor beta that can suppress HCV-specific T-cell responsesNadia 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... - CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashionSilke 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... - Innate immune response to encephalomyocarditis virus infection mediated by CD1dMark 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... - The A2aR adenosine receptor controls cytokine production in iNKT cellsMichael 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... - Peripheral blood progenitor cell product contains Th1-biased noninvariant CD1d-reactive natural killer T cells: implications for posttransplant survivalAngela 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... - Analysis of the major histocompatibility complex in graft rejection revisited by gene expression profilesKenneth 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... - Heterogeneity in phenotype and function of CD8+ and CD4/CD8 double-negative Natural Killer T cell subsets in sooty mangabeysNamita 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... - CD1d ligation on human monocytes directly signals rapid NF-kappaB activation and production of bioactive IL-12Simon 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... - Generation of antitumor invariant natural killer T cell lines in multiple myeloma and promotion of their functions via lenalidomide: a strategy for immunotherapyWeihua 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... - Exploiting regulatory T-cell populations for the immunotherapy of cancerHans 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... - Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 functionSebastian 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... - Isolation and functional use of human NK T cellsMark 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... - Natural killer T cell-based cancer immunotherapyHans 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 - Effects of the administration of high-dose interleukin-2 on immunoregulatory cell subsets in patients with advanced melanoma and renal cell cancerHans 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... 
Invariant natural killer T cells from rhesus macaque spleen and peripheral blood are phenotypically and functionally distinct populationsBalgansuren 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...- Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammalsAnneliese 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... - Hyporesponsiveness to natural killer T-cell ligand alpha-galactosylceramide in cancer-bearing state mediated by CD11b+ Gr-1+ cells producing nitric oxideKazuhiko 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... - The CD1d-binding glycolipid alpha-galactosylceramide enhances humoral immunity to T-dependent and T-independent antigen in a CD1d-dependent mannerGillian 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... - Gestation stage-dependent mechanisms of invariant natural killer T cell-mediated pregnancy lossJonathan 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... - Impaired cell surface expression of human CD1d by the formation of an HIV-1 Nef/CD1d complexSungyoo 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... - Phenotypic and functional characterization of long-term cultured rhesus macaque spleen-derived NKT cellsBalgansuren 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... - CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liverTony 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 Grants
- CD1D REACTIVE T CELLS IN BONE MARROW TRANSPLANTATIONMark 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. ..
- Innate-like hepatic CD1d-reative NKT cells:Liver DiseaseMark Exley; Fiscal Year: 2007..I. on acute HCV infection in chimpanzees, as well as on liver immunology and on 'NKT' cells in general. ..
- Innate-like hepatic CD1d-reative NKT cells:Liver DiseaseMark Exley; Fiscal Year: 2007..I. on acute HCV infection in chimpanzees, as well as on liver immunology and on 'NKT' cells in general. ..