Differential IL-2 expression defines developmental fates of follicular versus nonfollicular helper T cells

Abstract

(IL-)2 be or not to be? Immunological T follicular helper (T FH ) cells are a subpopulation of CD4 + T cells that support B cell antibody production and the establishment of B cell memory. By contrast, non-T FH cells orchestrate enhanced innate immune cell functions at sites of pathogen encounter. The factors underlying differentiation into a T FH or non-T FH cell remain poorly understood, though there is evidence to suggest that the T cell growth factor interleukin-2 (IL-2) may play a role. Using IL-2 reporter mice, DiToro et al. show that naïve CD4 + T cells that produce IL-2 are fated to become T FH cells, whereas nonproducers, which receive IL-2, become non-T FH cells. The CD4 + T cell–fate decision was linked to T cell receptor strength—only those naïve CD4 + T cells that received the highest T cell receptor signals were able to produce IL-2. Science , this issue p. eaao2933