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J Biol Chem ; 287(6): 4211-21, 2012 Feb 03.
Article in English | MEDLINE | ID: mdl-22167178

ABSTRACT

H(2)S is an endogenous signaling molecule that may act via protein sulfhydrylation to regulate various physiological functions. H(2)S 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 H(2)S production. Consistent with its increased production, H(2)S 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 H(2)S 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 H(2)S potentiate TCR-induced activation. Nanomolar levels of H(2)S (50-500 nM) enhance T cell activation assessed by CD69 expression, interleukin-2 expression, and CD25 levels. Exposure of T cells to H(2)S 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 H(2)S via increased expression of cystathionine γ-lyase and cystathionine ß-synthase. Disrupting this response by silencing these H(2)S producing enzymes impairs T cell activation, and proliferation and can be rescued by the addition of 300 nM H(2)S. Thus, H(2)S represents a novel autocrine immunomodulatory molecule in T cells.


Subject(s)
Air Pollutants/pharmacology , CD4-Positive T-Lymphocytes/immunology , Hydrogen Sulfide/pharmacology , Lymphocyte Activation/drug effects , Animals , Antigens, CD/genetics , Antigens, CD/immunology , Antigens, Differentiation, T-Lymphocyte/genetics , Antigens, Differentiation, T-Lymphocyte/immunology , Cell Proliferation/drug effects , Cystathionine beta-Synthase/genetics , Cystathionine beta-Synthase/immunology , Cystathionine gamma-Lyase/genetics , Cystathionine gamma-Lyase/immunology , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Gene Expression Regulation/immunology , Humans , Interleukin-2/genetics , Interleukin-2/immunology , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/immunology , Jurkat Cells , Lectins, C-Type/genetics , Lectins, C-Type/immunology , Lymphocyte Activation/genetics , Lymphocyte Activation/immunology , Mice , Mice, Transgenic
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