Hydrogen sulfide (H2S) is an endogenous signaling molecule that may act via protein sulfhydrylation to regulate various physiological functions. H2S is also a byproduct of dietary sulfate metabolism by gut bacteria. Inflammatory bowel diseases such as ulcerative colitis are associated with an increase in the colonization of the intestine by sulfate reducing bacteria along with an increase in H2S production. Consistent with its increased production, H2S is implicated as a mediator of ulcerative colitis both in its genesis or maintenance. As T cells are well established mediators of inflammatory bowel disease, we investigated the effect of H2S exposure on T cell activation. Using primary mouse T lymphocytes (CD3+), OT-II CD4+ T cells, and the human Jurkat T cell line, we show that physiological levels of H2S potentiate TCR-induced activation. Nanomolar levels of H2S (50-500 nM) enhance T cell activation assessed by CD69 expression, interleukin-2 expression, and CD25 levels. Exposure of T cells to H2S dose-dependently enhances TCR-stimulated proliferation with a maximum at 300 nM (30% increase, p <0.01). Furthermore, activation increases the capacity of T cells to make H2S via increased expression of cystathionine gamma-lyase and cystathionine beta-synthase. Disrupting this response by silencing these H2S producing enzymes impairs T cell activation, and proliferation and can be rescued by the addition of 300 nM H2S. Thus, H2S represents a novel autocrine immunomodulatory molecule in T cells.
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