Follicular helper T cells (TFH cells) and central memory T cells (TCM cells) share various key transcriptional features, which suggests there is some overlap in their developmental programs. In Nature Communications, Oestreich and colleagues show that cells with both TFH cell potential and TCM cell potential develop from the TH1 subset of helper T cells as IL-2 signaling wanes after an immune response winds down. These bipotential cells express receptors for both IL-6 and IL-7 and appear at later time points after infection. Signaling via the IL-6 receptor initiates a TFH cell transcriptional program, whereas IL-7 suppresses that and instead favors TCM cell development. The transcriptional regulator STAT5 downstream of the IL-7 receptor is responsible for repressing genes encoding products critical for TFH cell development, such as Bcl6. This work demonstrates a parsimonious mechanism by which both humoral immunological memory (via TFH cells) and cellular immunological memory (via TCM cells) can develop following an immune response.

Nat. Commun. (8 January 2016) doi:10.1038/ncomms10285