Chronic HIV-1 Infection Impairs Superantigen-Induced Activation of Peripheral CD4+CXCR5+PD-1+ Cells, With Relative Preservation of Recall Antigen-Specific Responses

J Acquir Immune Defic Syndr. 2017 Jan 1;74(1):72-80. doi: 10.1097/QAI.0000000000001152.

Abstract

Peripheral CD4+CXCR5+PD-1+ T cells are a putative circulating counterpart to germinal center T follicular helper (TFH) cells. They show both phenotypic and functional similarities to TFH cells, which provide necessary help for the differentiation of B cells to antibody-secreting plasmablasts. In this study, we evaluated the frequency, phenotypes, and responses of peripheral TFH-like (pTFH) cells to superantigen and recall antigen stimulation in 10 healthy and 34 chronically infected treatment-naive HIV-1+ individuals. There was no difference in the frequency of pTFH cells between HIV+ and HIV- individuals. Surface expression of ICOS, but not CD40L, was higher on pTFH cells at baseline in HIV+ individuals. Compared with HIV- individuals, pTFH cells from HIV+ individuals had decreased maximal expression of ICOS and CD40L in response to in vitro superantigen stimulation. This decreased response did not correlate with viral control, CD4 T-cell count, duration of infection, or the degree of neutralizing antibody breadth. Despite a decreased maximal response, pTFH responses to HIV Gag and tetanus toxoid recall antigens were preserved.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Ligand / analysis
  • HIV Infections / immunology*
  • Humans
  • Inducible T-Cell Co-Stimulator Protein / analysis
  • Lymphocyte Activation*
  • Programmed Cell Death 1 Receptor / analysis*
  • Receptors, CXCR5 / analysis*
  • Superantigens / immunology*
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology*

Substances

  • CXCR5 protein, human
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5
  • Superantigens
  • CD40 Ligand