Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation

Activation of CD4 + T cells leads to their polarization to various effector states. Goldrath and colleagues identify a role for the E-protein inhibitor Id2 in promoting T H 1 cell polarization over T FH cell polarization. Reciprocally, the transcription factor Bcl-6 represses Id2 expression in T FH cells. The differentiation of helper T cells into effector subsets is critical to host protection. Transcription factors of the E-protein and Id families are important arbiters of T cell development, but their role in the differentiation of the T H 1 and T FH subsets of helper T cells is not well understood. Here, T H 1 cells showed more robust Id2 expression than that of T FH cells, and depletion of Id2 via RNA-mediated interference increased the frequency of T FH cells. Furthermore, T H 1 differentiation was blocked by Id2 deficiency, which led to E-protein-dependent accumulation of effector cells with mixed characteristics during viral infection and severely impaired the generation of T H 1 cells following infection with Toxoplasma gondii . The T FH cell–defining transcriptional repressor Bcl6 bound the Id2 locus, which provides a mechanism for the bimodal Id2 expression and reciprocal development of T H 1 cells and T FH cells.