TIM-3 is Expressed on Activated Human CD4+ T Cells and Regulates Th1 and Th17 Cytokines

TIM-3 is a molecule selectively expressed on a subset of murine IFNγ-secreting 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 monoclonal antibodies specific for human TIM-3. We report that TIM-3 is expressed by a subset of activated CD4+ cells, and that anti-CD3/28 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 IFNγ, IL-17, IL-2, and IL-6, but not IL-10, IL-4, or TNFα, when stimulated with anti-CD3/28 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.