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

Michela Locci; Colin Havenar-Daughton; Elise Landais; Jennifer Wu; Mark A Kroenke; Cecilia L Arlehamn; Laura F Su; Rafael Cubas; Mark M Davis; Alessandro Sette; Elias K Haddad; International AIDS Vaccine Initiative Protocol C Principal Investigators; Pascal Poignard; Shane Crotty

doi:10.1016/j.immuni.2013.08.031

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.

Authors

Michela Locci¹, Colin Havenar-Daughton, Elise Landais, Jennifer Wu, Mark A Kroenke, Cecilia L Arlehamn, Laura F Su, Rafael Cubas, Mark M Davis, Alessandro Sette, Elias K Haddad; International AIDS Vaccine Initiative Protocol C Principal Investigators; Pascal Poignard, Shane Crotty

Affiliation

¹ Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.

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

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding