TY - JOUR
T1 - Cytotoxic CD8+ T Cells Expressing CXCR5 Are Detectable in HIV-1 Elite Controllers After Prolonged In Vitro Peptide Stimulation
AU - Adams, Philipp
AU - Iserentant, Gilles
AU - Servais, Jean Yves
AU - Vandekerckhove, Linos
AU - Vanham, Guido
AU - Seguin-Devaux, Carole
AU - the PhenoCure Study Group
N1 - Funding Information:
The authors would like to thank all patients who participated in the PhenoCure Study. We thank BioMARIC (Gent,Belgium), for providing the p24 ELISA kits and the RedCross Luxembourg, who provided blood from healthy volunteers to the study (protocol reference number:LIH-2018-0005). The following reagents were obtained through the HIV Reagent Program, Division of AIDS, NIAID, NIH: Peptide Array, Human Immunodeficiency Virus Type 1 Potential T-Cell Epitopes (PTE) Gag Region, ARP-11554, contributed by DAIDS/NIAID; Anti-Human CD3/8 Bi-specific Monoclonal, ARP-12277, contributed by Drs. Johnson Wong and Galit Alter.
Publisher Copyright:
© Copyright © 2021 Adams, Iserentant, Servais, Vandekerckhove, Vanham, Seguin-Devaux and the PhenoCure Study Group.
PY - 2021/2/24
Y1 - 2021/2/24
N2 - Antiretroviral therapy (ART) is not curative as HIV-1 persists in long-lived viral reservoirs. Consequently, patients are dependent on life-long drug adherence with possible side effects. To overcome these limitations strategies of a functional cure aim at ART free viral remission. In this study, we sought to identify detailed subsets of anti-viral CD8+ T cell immunity linked to natural long-term control of HIV-1 infection. Here, we analyzed HIV controllers and ART suppressed progressors for in vitro viral suppressive capacity (VSC) at baseline and after peptide stimulation. Functional properties and phenotypes of CD8+ T cells were assessed by IFN-γ ELISPOT and 18 color flow cytometry. HIV controllers showed significantly increased suppression at baseline as well as after peptide stimulation. IFN-γ secretion and the proliferation marker Ki67 positively correlated with VSC. Moreover, the detailed phenotype of three distinct multifunctional memory CD8+ T cell subsets were specific traits of HIV controllers of which two correlated convincingly with VSC. Our results underline the importance of multifunctional CD8+ T cell responses during natural control. Especially the role of CXCR5 expressing cytotoxic subsets emphasizes potential surveillance in sites of reservoir persistence and demand further study.
AB - Antiretroviral therapy (ART) is not curative as HIV-1 persists in long-lived viral reservoirs. Consequently, patients are dependent on life-long drug adherence with possible side effects. To overcome these limitations strategies of a functional cure aim at ART free viral remission. In this study, we sought to identify detailed subsets of anti-viral CD8+ T cell immunity linked to natural long-term control of HIV-1 infection. Here, we analyzed HIV controllers and ART suppressed progressors for in vitro viral suppressive capacity (VSC) at baseline and after peptide stimulation. Functional properties and phenotypes of CD8+ T cells were assessed by IFN-γ ELISPOT and 18 color flow cytometry. HIV controllers showed significantly increased suppression at baseline as well as after peptide stimulation. IFN-γ secretion and the proliferation marker Ki67 positively correlated with VSC. Moreover, the detailed phenotype of three distinct multifunctional memory CD8+ T cell subsets were specific traits of HIV controllers of which two correlated convincingly with VSC. Our results underline the importance of multifunctional CD8+ T cell responses during natural control. Especially the role of CXCR5 expressing cytotoxic subsets emphasizes potential surveillance in sites of reservoir persistence and demand further study.
KW - CXCR5 CD8 T cells + +
KW - HIV controllers
KW - elite controllers
KW - functional cure
KW - multifunctional CD8 T cells
KW - viral suppressive capacity
UR - http://www.scopus.com/inward/record.url?scp=85102359509&partnerID=8YFLogxK
UR - https://www.ncbi.nlm.nih.gov/pubmed/33717056
U2 - 10.3389/fimmu.2020.622343
DO - 10.3389/fimmu.2020.622343
M3 - Article
C2 - 33717056
AN - SCOPUS:85102359509
SN - 1664-3224
VL - 11
SP - 622343
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 622343
ER -