T follicular regulatory cells in mice and men

It has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal centre (GC) reaction where affinity maturation and isotype switching occur. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T-cell population also found within GCs but with regulatory function and characteristics. Tfr cells have been identified in mice and humans as simultaneously presenting characteristics of T follicular cells (namely CXCR5 expression) and regulatory T cells (including Foxp3 expression). These Tfr cells have been implicated in the regulation of the magnitude of the GC reaction, as well as in protection from immune-mediated pathology.