Lymphocyte differentiation articles from across Nature Portfolio

Wang and colleagues revealed how oleic acid produced by thymic epithelial cells could affect the developing thymocytes to differentiate into peripheral regulatory T cells.

Wu and colleagues identify gene networks and transcription factors that control the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8⁺ CAR T cells.

Follicular helper T cells play critical roles in the formation of high affinity antibody responses, but the signals involved in the development of these cells after initial differentiation are poorly understood. Here Podestà, Cavazzoni and colleagues characterise transitionary phases of follicular helper T cell development and how progression through these stages is linked to humoral immunity.

Although T cells proliferate at an exceptionally fast rate following activation, the mechanisms sustaining such fast proliferation remain unclear. Here, the authors demonstrate that c-Myc upregulates the E3 ubiquitin ligase Cul4b to reduce replication stress in CD8⁺ T cells, allowing massive clonal expansion and viral clearance.

The transcription factor NFAT5 regulates T cell exhaustion, a dysfunctional state caused by chronic exposure to antigen and other signals, during cancer but not during chronic viral infection.

A preprint by Le Coz et al. identifies that human T follicular regulatory cells with differences in T cell suppressive and B cell helper capacities can be derived from the regulatory T cell lineage or the T follicular helper cell lineage.

Exhausted effector T cells accumulate in tumors and are the intended targets of cancer immunotherapy. New data suggest that upon infiltration and subsequent exhaustion in the tumor microenvironment, these T cells can take on an immunosuppressive function — and work against the immune response to cancer.