title: Impact of Chronic HIV/SIV Infection on T Follicular Helper Cell Subsets and Germinal Center Homeostasis.
abstract: The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has renewed optimism for developing an effective vaccine against HIV-1. The generation of most bNAbs requires multiple rounds of B cell receptor affinity maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their production. However, less than 1% of HIV-infected patients develop bNAbs that arise late in the course of infection, indicating probable Tfh and B cell dysfunctions in this context. Since the last few years, many studies have characterized Tfh cells from lymph nodes and spleen of HIV-infected individuals and SIV-infected macaques. Various lymphoid Tfh cell subsets have been identified, including precursor Tfh (pTfh), germinal center Tfh (GC Tfh), and the regulatory counterpart of Tfh cells, the follicular regulatory T cells. The latter have been reported to play a crucial role in the control of T and B cell crosstalk and GC reactions. More recently, circulating Tfh-like cells (cTfh) have been identified. Meanwhile, advances in single-cell technologies have made possible to analyze the transcriptional profiles of low abundant cells, such as Tfh populations. Using transcriptional signatures, we review here the impact of chronic SIV/HIV infection on Tfh, GC Tfh, pTfh, and cTfh differentiation and helper T cell functions with regard to their capacity to induce efficient B cell maturation. We will explore some hypothesis to explain the increased proportion of Tfh cells reported in chronically infected individuals and the impact on HIV pathogenesis.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, U1135, CNRS 8255 , Paris , France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Graff-Dubois
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, U1135, CNRS 8255 , Paris , France.
authors.forename: Angeline
authors.initials: A
authors.lastname: Rouers
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, U1135, CNRS 8255 , Paris , France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Moris
keywords: HIV; SIV; Tfh cell differentiation; Tfh cell dynamics; germinal center reaction