Mucosal T follicular helper cells in SIV-infected rhesus macaques: contributing role of IL-27

Mucosal Immunol. 2019 Jul;12(4):1038-1054. doi: 10.1038/s41385-019-0174-0. Epub 2019 May 21.


Mesenteric lymph nodes (MLNs), that drain the large and small intestine, are critical sites for the induction of oral tolerance. Although depletion of CD4 T cells in the intestinal lamina propria is a hallmark of HIV infection, CD4 T cell dynamics in MLNs is less known due to the lack of accessibility to these LNs. We demonstrate the early loss of memory CD4 T cells, including T follicular helper cells (Tfh) and a remodeling of MLN architecture in SIV-infected rhesus macaques (RMs). Along with the loss of Tfh cells, we observe the loss of memory B cells and of germinal center B cells. Tfh cells display a Th1 profile with increased levels of the transcription factors that negatively impact on Tfh differentiation and of Stat5 phosphorylation. MLNs of SIV-infected RMs display lower mRNA transcripts encoding for IL-12, IL-23, and IL-35, whereas those coding for IL-27 are not impaired in MLNs. In vitro, IL-27 negatively impacts on Tfh cells and recapitulates the profile observed in SIV-infected RMs. Therefore, early defects of memory CD4 T cells, as well of Tfh cells in MLNs, which play a central role in regulating the mucosal immune response, may have major implications for Aids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Biomarkers
  • Gene Expression
  • Immunohistochemistry
  • Immunologic Memory
  • Immunophenotyping
  • Interleukin-27 / genetics
  • Interleukin-27 / metabolism*
  • Intraepithelial Lymphocytes / immunology*
  • Intraepithelial Lymphocytes / metabolism*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocyte Count
  • Macaca mulatta
  • Phosphorylation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / metabolism*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*


  • Biomarkers
  • Interleukin-27
  • RNA, Messenger