Macroautophagy in T lymphocyte development and function

Abstract

Macroautophagy (referred to as autophagy) is a fundamental intracellular process characterized by the sequestration of cytoplasmic compartments through double-membrane vesicles, termed autophagosomes. Recent studies have established important roles of autophagy in regulating T lymphocyte development and function. Resting T lymphocytes have basal levels of autophagy that is upregulated by T cell receptor stimulation. Several specific knockout or transgenic models have been developed during the past few years, and it has been revealed that autophagy plays an essential role in regulating thymocyte selection, peripheral T cell survival, and proliferation. The regulation of T cell development and function by autophagy is mediated through its role in regulating self-antigen presentation, intracellular organelle homeostasis, and energy production. Here we will review the current findings concerning how autophagy regulates T cell function, as well as compare different models in studying autophagy in T lymphocytes.

Keywords: T lymphocyte; apoptosis; autophagy; organelle homeostasis; thymocyte selection.

Figure 1

Autophagy in T lymphocytes. Published results indicate that TCR engagement is a strong inducer of autophagy in primary T cells. Although autophagy is induced by the PtdIns3k complex in many types of cells, the role of this complex in autophagy induction in T lymphocytes may not be the same as in other cells. Vps34 is dispensable for autophagy induction in T cells while it promotes T cell survival by regulating IL-7Rα surface expression. The role of Beclin-1 in T cell autophagy induction remains to be further defined. However, the two autophagosome processing pathways: Atg5–Atg12 conjugation and LC3 processing are essential for autophagy induction as deleting Atg3, Atg5, and Atg7 all results in impaired autophagy in T cells. Furthermore, FADD, the death adaptor protein in the extrinsic death pathway, may play a key role in mediating a crosstalk between the apoptosis and autophagy pathways.