Immunology

Highlights

 

•T effector cell differentiation depends on de novo fatty acid (FA) synthesis.•CD8+ T memory cell development and function depend on both FA synthesis and oxidation.•FA synthesis and oxidation are determinants for CD4+ T effector versus Treg cell development.•These pathways may present therapeutic targets for modulating T cell responses in vivo.

 

The specific regulation of cellular metabolic processes is of major importance for directing immune cell differentiation and function. We review recent evidence indicating that changes in basic cellular lipid metabolism have critical effects on T cell proliferation and cell fate decisions. While induction of de novo fatty acid (FA) synthesis is essential for activation-induced proliferation and differentiation of effector T cells, FA catabolism via β-oxidation is important for the development of CD8+ T cell memory as well as for the differentiation of CD4+ regulatory T cells. We consider the influence of lipid metabolism and metabolic intermediates on the regulation of signaling and transcriptional pathways via post-translational modifications, and discuss how an improved understanding of FA metabolism may reveal strategies for manipulating immune responses towards therapeutic outcomes.

Via Krishan Maggon

Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC).

Via Krishan Maggon

Abstract

The organization of the thymus into distinct cortical and medullary regions enables it to control the step-wise migration and development of immature T-cell precursors. Such a process provides access to specialized cortical and medullary thymic epithelial cells at defined stages of maturation, ensuring the generation of self-tolerant and MHC-restricted conventional CD4+ and CD8+ αβ T cells. The migratory cues and stromal cell requirements that regulate the development of conventional αβ T cells have been well studied. However, the thymus also fosters the generation of several immunoregulatory T-cell populations that form key components of both innate and adaptive immune responses. These include Foxp3+ natural regulatory T cells, invariant γδ T cells, and CD1d-restricted invariant natural killer T cells (iNKT cells). While less is known about the intrathymic requirements of these nonconventional T cells, recent studies have highlighted the importance of the thymus medulla in their development. Here, we review recent findings on the mechanisms controlling the intrathymic migration of distinct T-cell subsets, and relate this to knowledge of the microenvironmental requirements of these cells.

Via Krishan Maggon