Regulatory roles of IL-10-producing T follicular cells

Abstract

Mucosal lymphoid tissues like human tonsils are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T cells (TFH) and Foxp3+ follicular regulatory T cells (TFR). Here we describe a subset of human tonsillar follicular T cells (TF) identified by expression of TFH cell markers and CD25 that are the main source of T cell-derived IL-10 in the follicle. Despite lack of FOXP3 expression, CD25+ TF cells resemble Tregs in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. IL-10 boosts conversion of human tonsil TFH cells into FOXP3-expressing cells, possibly promoting peripherally- induced TFR cells at mucosal sites. CD25+ TF cell-derived IL-10 inhibits B cell class-switching to IgE. In children, serum total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10-producing TF cells but not with total Tregs, TFR or IL-10-producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.