DCs regulate T_FH generation

Follicular helper T cells (T_FH cells) contribute to germinal-center reactions to promote plasma-cell generation and antibody affinity maturation. In Nature, Cyster and colleagues identify a regulatory role for CD4⁺ dendritic cells (DCs) in T_FH differentiation. Naive CD4⁺ T cells upregulate their expression of EBI2, a G-protein-coupled receptor, after immunization or in vitro activation. EBI2 directs migration to the B cell–T cell interface and interaction with antigen-presenting CD4⁺ DCs. EBI2-deficient T cells proliferate less and form fewer T_FH cells than do wild-type T cells. Interestingly, activated CD4⁺ DCs express the cytokine receptor CD25, which limits the availability of interleukin 2 (IL-2). This sequestration of IL-2 favors T_FH differentiation over differentiation into the T_H1 subset of helper T cells. Specific loss of CD25 expression in DCs likewise leads to defective generation of T_FH cells. These findings show that DC–T cell interactions are more complex and involve feedback regulation that influences T cell polarization.

Nature (5 May 2016) doi:10.1038/nature17947