Autophagy and adaptive immunity.

Abstract

Autophagy plays an important role in maintaining intracellular homeostasis by promoting the transit of cytoplasmic material, such as proteins, organelles and pathogens, for degradation within acidic organelles. Yet, in immune cells, autophagy pathways serve an additional role in facilitating intracellular surveillance for pathogens and changes in self. Autophagy pathways can modulate key steps in the development of innate and adaptive immunity. In terms of adaptive immunity, autophagy regulates the development and survival of lymphocytes as well as the modulation of antigen processing and presentation. Specialized forms of autophagy may be induced by some viral pathogens, providing a novel route for major histocompatibility complex (MHC) class I antigen presentation and enhanced CD8(+) T-cell responses. Autophagy induction in target cells also increases their potential to serve as immunogens for dendritic cell cross-presentation to CD8(+) T cells. The requirement for autophagy in MHC class II presentation of cytoplasmic and nuclear antigens is well established, yet recent studies also point to a critical role for autophagy in modulating CD4(+) T-cell responses to phagocytosed pathogens. Autophagy pathways can also modulate the selection and survival of some CD4(+) T cells in the thymus. However, much still remains to be learned mechanistically with respect to how autophagy and autophagy-linked genes regulate pathogen recognition and antigen presentation, as well as the development and survival of immune cells.