mTORC2 in T Lymphocyte Development and Proliferation

This is the authors' abstract. We don't add key points for this paper.

PDK1 and its downstream target Akt contribute both to pre‐TCR and TCR signal transduction important for proliferation and survival of thymocytes undergoing β‐selection or mature T cells. Mammalian target of rapamycin (mTOR) controls various cell functions and is a target of immunosuppressant drugs. Recent biochemical studies suggest that mTOR complex 2 (mTORC2) may be the exclusive kinase for phosphorylation of S473 in Akt. However, the role of mTORC2 in T lineage is not known. Here, we show that mTORC2 regulates T cell development and cytokine‐induced proliferation. To assess the consequences of reduced activity of mTORC2 in T lymphocytes, we generated mice with T lineage‐specific depletion of rictor, an indispensible component of mTORC2. The results indicate that mTORC2 is required for normal DN/DP transition and suggest a role in positive selection process. Furthermore, mTORC2 haplo‐insufficiency in peripheral T cells impairs cell cycle progression induced by cytokines whose receptor share the common γ chain without affecting survival. Overall, these findings indicate that mTORC2 is a crucial signal relay in T cell development and homeostasis, presumably by regulating phosphorylation status of Akt.