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Sci. Signal., 20 December 2011
Vol. 4, Issue 204, p. ra90
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-B. 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.
Citation: A. Schmidt, N. Oberle, E.-M. Weiß, D. Vobis, S. Frischbutter, R. Baumgrass, C. S. Falk, M. Haag, B. Brügger, H. Lin, G. W. Mayr, P. Reichardt, M. Gunzer, E. Suri-Payer, P. H. Krammer, Human Regulatory T Cells Rapidly Suppress T Cell Receptor–Induced Ca2+, NF-B, and NFAT Signaling in Conventional T Cells. Sci. Signal.4, ra90 (2011).