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Early Th1 cell differentiation is marked by a Tfh cell-like transition.

Nakayamada, Shingo; Kanno, Yuka; Takahashi, Hayato; Jankovic, Dragana; Lu, Kristina T; Johnson, Thomas A; Sun, Hong-wei; Vahedi, Golnaz; Hakim, Ofir; Handon, Robin; Schwartzberg, Pamela L; Hager, Gordon L; O'Shea, John J.
Immunity; 35(6): 919-31, 2011 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-22195747
Follicular helper T (Tfh) cells comprise an important subset of helper T cells; however, their relationship with other helper lineages is incompletely understood. Herein, we showed interleukin-12 acting via the transcription factor STAT4 induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells. However, STAT4 also induced the transcription factor T-bet. With ChIP-seq, we defined the genome-wide targets of T-bet and found that it repressed Bcl6 and other markers of Tfh cells, thereby attenuating the nascent Tfh cell-like phenotype in the late phase of Th1 cell specification. Tfh-like cells were rapidly generated after Toxoplasma gondii infection in mice, but T-bet constrained Tfh cell expansion and consequent germinal center formation and antibody production. Our data argue that Tfh and Th1 cells share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh cell functionalities, promoting full Th1 cell differentiation.
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