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Nat Immunol. 2015 Sep;16(9):991-9. doi: 10.1038/ni.3229. Epub 2015 Jul 27.

The transcription factor TCF-1 initiates the differentiation of T(FH) cells during acute viral infection.

Author information

1
Institute of Immunology, Third Military Medical University, Chongqing, China.
2
1] Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University, Yangzhou, China. [2] Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.

Abstract

Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of T(FH) differentiation and the effector function of differentiated T(FH) cells during acute viral infection. Mechanistically, TCF-1 bound directly to the Bcl6 promoter and Prdm1 5' regulatory regions, which promoted Bcl-6 expression but repressed Blimp1 expression. TCF-1-null T(FH) cells upregulated genes associated with non-T(FH) cell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the differentiation of T(FH) cells during acute viral infection.

PMID:
26214740
DOI:
10.1038/ni.3229
[Indexed for MEDLINE]

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