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J Immunol. 2016 Mar 1;196(5):2015-9. doi: 10.4049/jimmunol.1501841. Epub 2016 Feb 5.

Cutting Edge: NFAT Transcription Factors Promote the Generation of Follicular Helper T Cells in Response to Acute Viral Infection.

Author information

1
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; gustavo.martinez@rosalindfranklin.edu.
2
Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037;
3
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
4
Genomics Core, The Scripps Research Institute, Jupiter, FL, 33458;
5
Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037; Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037;
6
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093; and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037.

Abstract

Follicular CD4(+) Th (Tfh) cells provide B cell help in germinal center reactions that support class switching, somatic hypermutation, and the generation of high-affinity Abs. In this article, we show that deficiency in NFAT1 and NFAT2 in CD4(+) T cells leads to impaired germinal center reactions upon viral infection because of reduced Tfh cell differentiation and defective expression of proteins involved in T/B interactions and B cell help, including ICOS, PD-1, and SLAM family receptors. Genome-wide chromatin immunoprecipitation data suggest that NFAT proteins likely directly participate in regulation of genes important for Tfh cell differentiation and function. NFAT proteins are important TCR and Ca(2+)-dependent regulators of T cell biology, and in this article we demonstrate a major positive role of NFAT family members in Tfh differentiation.

PMID:
26851216
PMCID:
PMC4761453
[Available on 2017-03-01]
DOI:
10.4049/jimmunol.1501841
[Indexed for MEDLINE]
Free PMC Article

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