Antiviral and regulatory T cell immunity in a patient with stromal interaction molecule 1 deficiency
21.12.2011
Fuchs S, Rensing-Ehl A, Speckmann C, Bengsch B, Schmitt-Graeff A, Bondzio I, Maul-Pavicic A, Bass T, Vraetz T, Strahm B, Ankermann T, Benson M, Caliebe A, Fölster-Holst R, Kaiser P, Thimme R, Schamel WW, Schwarz K, Feske S, Ehl S.
J Immunol. 2012 Feb 1;188(3):1523-33.
In this publication we analyzed the activation of T cells in a human patient with a mutation in a protein called stromal interaction molecule 1 (STIM1). STIM1 controls store-operated calcium entry from the outside to the cytosol and its absence is associated with immune dysregulation and immunodeficiency. Using the patient cells, we show that STIM1-deficiency completely abolished store-operated calcium entry in T cells. T cell proliferation was impaired in vitro, however, antiviral T cell populations were generated in vivo. The deficient T cells showed normal antiviral cytotoxicity,
demonstrating that STIM1 was dispensable for the cytotoxic activity of T cells. In contrast, cytokine production was impaired. Regulatory T cells were present, and suppression of proliferative responses by STIM1 deficient Treg in vitro was normal.
These observations indicate that for several read-outs of antiviral T cell immunity, store-operated calcium entry is not limiting. Further, our results question a key role for store-operated calcium entry in the development and function of Treg as the basis of autoimmunity in STIM1 deficiency.
