title: TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines.
abstract: TIM-3 is a molecule selectively expressed on a subset of murine IFN-gamma-secreting T helper 1 (Th1) cells but not Th2 cells, and regulates Th1 immunity and tolerance in vivo. At this time little is known about the role of TIM-3 on human T cells. To determine if TIM-3 similarly identifies and regulates Th1 cells in humans, we generated a panel of mAb specific for human TIM-3. We report that TIM-3 is expressed by a subset of activated CD4(+) cells, and that anti-CD3/anti-CD28 stimulation increases both the level of expression as well as the number of TIM-3(+) T cells. We also find that TIM-3 is expressed at high levels on in vitro polarized Th1 cells, and is expressed at lower levels on Th17 cells. In addition, human CD4(+) T cells secreted elevated levels of IFN-gamma, IL-17, IL-2, and IL-6, but not IL-10, IL-4, or TNF-alpha, when stimulated with anti-CD3/anti-CD28 in the presence of TIM-3-specific, putative antagonistic antibodies. This was not mediated by differences in proliferation or cell death, but rather by induction of cytokines at the transcriptional level. These results suggest that TIM-3 is a negative regulator of human T cells and regulates Th1 and Th17 cytokine secretion.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Hastings
authors.forename: David E
authors.initials: DE
authors.lastname: Anderson
authors.forename: Nasim
authors.initials: N
authors.lastname: Kassam
authors.forename: Ken
authors.initials: K
authors.lastname: Koguchi
authors.forename: Edward A
authors.initials: EA
authors.lastname: Greenfield
authors.forename: Sally C
authors.initials: SC
authors.lastname: Kent
authors.forename: Xin Xiao
authors.initials: XX
authors.lastname: Zheng
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D037161:Galectins / Q000276:immunology / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D007155:Immunologic Factors; C105032:LGALS9 protein, human; D008565:Membrane Proteins
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