TRPM2 Is Not Required for T-Cell Activation and Differentiation.

Antigen recognition by the T-cell receptor induces a cytosolic Ca signal that is crucial for T-cell function. The Ca channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca 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 from studies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca 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 stimulation , and WT CD4 and CD8 T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation of CD8 T cells and unimpaired differentiation of CD4 T cells into Th1, Th17, and Treg cells under specific polarizing conditions. , and WT CD8 T cells showed equal specific responses to after infection of WT and mice and after transfer of WT and 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 and CD4 T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.