Regulatory roles of IL-10-producing human follicular T cells

Mucosal lymphoid tissues such as human tonsil 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 (T_FH) cells and FOXP3⁺ follicular regulatory T (T_FR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of T_FH markers and CD25 that are the main source of follicular T (T_F) cell-derived IL-10. Despite lack of FOXP3 expression, CD25⁺ T_F cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25⁺ T_F cell-derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25⁺ T_F cells and IL-10-producing T_F cells but not with total T reg cells, T_FR, or IL-10-producing T cells. Thus, CD25⁺ T_F cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.