A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet
Xin, A; Masson, F; Liao, Y; Preston, S; Guan, T; Gloury, R; Olshansky, M; Lin, JX; Li, P; Speed, TP; Smyth, GK; Ernst, M; Leonard, WJ; Pellegrini, M; Kaech, SM; Nutt, SL; Shi, W; Belz, GT; Kallies, A
T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8+ T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. The loss of both T-bet and Blimp-1 leads to abrogated cytotoxic function and ectopic IL-17 production in CD8+ T cells. Overall, our data reveal two major overlapping pathways of effector differentiation governed by the availability of Blimp-1 and T-bet and suggest a model for cytokine-induced transcriptional changes that combine, quantitatively and qualitatively, to promote robust effector CD8+ T cell differentiation.
Bioinformatics; Infection and Immunity; Molecular Immunology