Inadequate T follicular cell help impairs B cell immunity during HIV infection

Nat Med. 2013 Apr;19(4):494-9. doi: 10.1038/nm.3109. Epub 2013 Mar 10.


The majority of HIV-infected individuals fail to produce protective antibodies and have diminished responses to new immunizations. We report here that even though there is an expansion of follicular helper T (TFH) cells in HIV-infected individuals, the cells are unable to provide adequate B cell help. We found a higher frequency of programmed cell death ligand 1 (PD-L1)(+) germinal center B cells from lymph nodes of HIV-infected individuals suggesting a potential role for PD-1-PD-L1 interaction in regulating TFH cell function. In fact, we show that engagement of PD-1 on TFH cells leads to a reduction in cell proliferation, activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine secretion. Blocking PD-1 signaling enhances HIV-specific immunoglobulin production in vitro. We further show that at least part of this defect involves IL-21, as addition of this cytokine rescues antibody responses and plasma cell generation in vitro. Our results suggest that deregulation of TFH cell-mediated B cell help diminishes B cell responses during HIV infection and may be related to PD-1 triggering on TFH cells. These results demonstrate a role for TFH cell impairment in HIV pathogenesis and suggest that enhancing their function could have a major impact on the outcome and control of HIV infection, preventing future infections and improving immune responses to vaccinations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • B7-H1 Antigen / physiology
  • HIV Infections / immunology*
  • Humans
  • Immunoglobulin G / immunology
  • Interleukins / physiology
  • Lymphocyte Activation / immunology
  • Lymphocyte Activation / physiology
  • Macaca mulatta
  • Male
  • Middle Aged
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / physiology


  • B7-H1 Antigen
  • Immunoglobulin G
  • Interleukins
  • interleukin-21