ICOS-ICOSL interaction-independent Tfh cell differentiation of Foxp1-deficient CD4+ T cells (LYM8P.629)

Abstract CD4+ T follicular helper (Tfh) cells are essential for germinal center (GC) and long-lived antibody responses. Studies have shown that the deletion of the inducible T cell co-stimulator (ICOS) results in severe defects of Tfh cell differentiation and germinal center responses. It has been shown that ICOS-ICOS ligand (ICOSL) interaction is not only critical for Bcl6 induction, but also essential for the follicular recruitment of activated CD4+ T cells by follicular bystander B cells that collectively form an ICOS-engaging field. Previously we have identified transcription factor Foxp1 as a critical negative regulator of Tfh cell differentiation. We now provide evidence showing that naïve CD4+ T cells deficient in both Foxp1 and ICOS still differentiate into Tfh cells at high frequencies with Bcl6 induced. Such results are confirmed in ICOSL-deficient recipient mice, in which Foxp1-deficient CD4+ T cell differentiate into Tfh cells. Taken together, our studies suggest that Foxp1 plays a profoundly dominant role in regulating Tfh cell differentiation.