Phospholipase Cγ1 is essential for T cell development, activation, and tolerance

Phospholipase C gamma 1 (PLC gamma 1) is an important signaling effector of T cell receptor (TCR). To investigate the role of PLC gamma 1 in T cell biology, we generated and examined mice with T cell-specific deletion of PLC gamma 1. We demonstrate that PLC gamma 1 deficiency affects positive and negative selection, significantly reduces single-positive thymocytes and peripheral T cells, and impairs TCR-induced proliferation and cytokine production, and the activation of ERK, JNK, AP-1, NFAT, and NF-kappa B. Importantly, PLC gamma 1 deficiency impairs the development and function of FoxP3(+) regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLC gamma 1 is essential for T cell development, activation, and tolerance.