TRPM2 Is Not Required for T-Cell Activation and Differentiation

Abstract

Antigen recognition by the T-cell receptor induces a cytosolic Ca2+signal that is crucial for T-cell function. The Ca2+channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca2+through the plasma membrane of T cells. Therefore, it was suggested that TRPM2 is involved in T-cell activation and differentiation. However, these results are largely derived fromin vitrostudies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca2+signaling in T cells remains unclear. Here, we use TRPM2-deficient mice to investigate the function of TRPM2 in T-cell activation and differentiation. In response to TCR stimulationin vitro,Trpm2-/-and WT CD4+and CD8+T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation ofTrpm2-/-CD8+T cells and unimpaired differentiation of CD4+T cells into Th1, Th17, and Treg cells under specific polarizing conditions.In vivo,Trpm2-/-and WT CD8+T cells showed equal specific responses toListeria monocytogenesafter infection of WT andTrpm2-/-mice and after transfer of WT andTrpm2-/-CD8+T cells into infected recipients. CD4+T-cell responses were investigated in the model of anti-CD3 mAb-induced intestinal inflammation, which allows analysis of Th1, Th17, Treg, and Tr1-cell differentiation. Here again, we detected similar responses of WT andTrpm2-/-CD4+T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.