A) Naïve T cells express high levels of Tcf1, which are downregulated upon Th1 effector cell differentiation. A subset of effector Th1 will re-express Tcf1 acquiring a memory phenotype, which is later crucial to drive a second wave of Th1 effector response. B) Tcf1hi naïve T cells differentiate into Tcf1lo Th17 cells generating a first wave of effector cells. Tcf1 is then re-expressed in a subset of cells to generate a stem-like Th17 subset. This Th17 stem-like population can either self-renew (1); give rise to effector Th17, which mainly produce IL-17A, in response to environmental cues or asymmetric partitioning of Tcf1 (2); or produce highly tissue destructive Th17/Th1-like cells that are polyfunctional and can secrete IL-17A, IFNγ, GM-CSF, and TNFα (3).
Tcf, T cell factor; Th1, T helper 1; Th17, T helper 17; IL-17A, interleukin 17; IFNγ, interferon gamma; GM-CSF, granulocyte-macrophage colony-stimulating factor; TNFα, tumor necrosis factor alpha.