Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses

Immunity. 2013 Oct 17;39(4):758-69. doi: 10.1016/j.immuni.2013.08.031. Epub 2013 Sep 12.

Abstract

The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. It is now conceivable that an antibody-dependent HIV vaccine might be possible, given the discovery of HIV broadly neutralizing antibodies (bnAbs) in some HIV-infected individuals. However, these antibodies are difficult to develop and have characteristics indicative of a high degree of affinity maturation in germinal centers (GCs). CD4⁺ T follicular helper (Tfh) cells are specialized for B cell help and necessary for GCs. Therefore, the development of HIV bnAbs might depend on Tfh cells. Here, we identified in normal individuals a subpopulation of circulating memory PD-1⁺CXCR5⁺CD4⁺ T cells that are resting memory cells most related to bona fide GC Tfh cells by gene expression profile, cytokine profile, and functional properties. Importantly, the frequency of these cells correlated with the development of bnAbs against HIV in a large cohort of HIV⁺ individuals.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Neutralizing / biosynthesis*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • Gene Expression
  • Gene Expression Profiling
  • Germinal Center / immunology
  • Germinal Center / pathology
  • Germinal Center / virology
  • HIV Antibodies / biosynthesis*
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunity, Humoral
  • Immunologic Memory
  • Molecular Sequence Data
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology*
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / immunology*
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology
  • T-Lymphocytes, Helper-Inducer / virology

Substances

  • Antibodies, Neutralizing
  • CXCR3 protein, human
  • CXCR5 protein, human
  • HIV Antibodies
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR3
  • Receptors, CXCR5

Associated data

  • GENBANK/GSE50390
  • GENBANK/GSE50392