Research ArticleImmunology

Human Regulatory T Cells Rapidly Suppress T Cell Receptor–Induced Ca2+, NF-κB, and NFAT Signaling in Conventional T Cells

Sci. Signal.  20 Dec 2011:
Vol. 4, Issue 204, pp. ra90
DOI: 10.1126/scisignal.2002179

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Suppressing Calcium Suppresses T Cells

Regulatory T cells (Tregs) are required to keep conventional T cells in check, and disruption of the generation or function of Tregs leads to autoimmunity. Conversely, Tregs can have a deleterious effect by dampening antitumor responses of T cells. Thus, improved understanding of the mechanisms by which Tregs inhibit T cell receptor (TCR)–induced responses in conventional T cells would help to develop better therapies against autoimmune disorders and cancer. Schmidt et al. found that TCR-induced, Ca2+-dependent signaling in human conventional T cells that were incubated with Tregs was inhibited compared to that in nonsuppressed T cells, which led to defective activation of the transcription factors NFAT and NF-κB. In contrast, Ca2+-independent signaling was unaffected. Suppressed signaling persisted after the Tregs were removed from cocultures. Increasing the intracellular concentration of Ca2+ in conventional T cells reversed the inhibitory effects of Tregs. Together, these data suggest that inhibition of Ca2+ signaling is critical for the suppressive effects of Tregs.