Id2-Mediated Inhibition of E2A Represses Memory CD8(+) T Cell Differentiation
Masson, F; Minnich, M; Olshansky, M; Bilic, I; Mount, AM; Kallies, A; Speed, TP; Busslinger, M; Nutt, SL; Belz, GT
JOURNAL OF IMMUNOLOGY
The transcription factor inhibitor of DNA binding (Id) 2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors T cell memory recall capacity. As a result of the defective effector differentiation, Id2-deficient CD8(+) T cells fail to induce sufficient Tbx21 expression to generate short-lived effector CD8(+) T cells. Our findings reveal that the Id2/E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation. The Journal of Immunology, 2013, 190: 4585-4594.
AMER ASSOC IMMUNOLOGISTS
PROTEIN TRANSCRIPTION FACTORS; FUNCTIONAL MATURATION; ID PROTEINS; EXPRESSION; EFFECTOR; MICE; BET; INFLAMMATION; MAINTENANCE; PRECURSOR