Early Th1 Cell Differentiation Is Marked by a Tfh Cell-like Transition

Shingo Nakayamada, Yuka Kanno, Hayato Takahashi, Dragana Jankovic, Kristina T. Lu, Thomas A. Johnson, Hong wei Sun, Golnaz Vahedi, Ofir Hakim, Robin Handon, Pamela L. Schwartzberg, Gordon L. Hager, John J. O'Shea

Research output: Contribution to journalArticlepeer-review

313 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)919-931
Number of pages13
JournalImmunity
Volume35
Issue number6
DOIs
Publication statusPublished - 2011 Dec 23
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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