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Nat Immunol. 2015 Jan;16(1):118-28. doi: 10.1038/ni.3036. Epub 2014 Nov 17.

TLR7 induces anergy in human CD4(+) T cells.

Author information

1
Department of Neurology and Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
2
Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA.

Abstract

The recognition of microbial patterns by Toll-like receptors (TLRs) is critical for activation of the innate immune system. Although TLRs are expressed by human CD4(+) T cells, their function is not well understood. Here we found that engagement of TLR7 in CD4(+) T cells induced intracellular calcium flux with activation of an anergic gene-expression program dependent on the transcription factor NFATc2, as well as unresponsiveness of T cells. As chronic infection with RNA viruses such as human immunodeficiency virus type 1 (HIV-1) induces profound dysfunction of CD4(+) T cells, we investigated the role of TLR7-induced anergy in HIV-1 infection. Silencing of TLR7 markedly decreased the frequency of HIV-1-infected CD4(+) T cells and restored the responsiveness of those HIV-1(+) CD4(+) T cells. Our results elucidate a previously unknown function for microbial pattern-recognition receptors in the downregulation of immune responses.

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PMID:
25401424
PMCID:
PMC4413902
DOI:
10.1038/ni.3036
[Indexed for MEDLINE]
Free PMC Article

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