TLR7 induces anergy in human CD4(+) T cells

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Calcium / immunology
  • Clonal Anergy / immunology
  • Down-Regulation
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation
  • NFATC Transcription Factors / immunology
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Toll-Like Receptor 7 / antagonists & inhibitors
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology*


  • NFATC Transcription Factors
  • NFATC2 protein, human
  • RNA, Small Interfering
  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Calcium