Author:
Scharf Lydia,Pedersen Christina B.,Johansson Emil,Lindman Jacob,Olsen Lars R.,Buggert Marcus,Wilhelmson Sten,Månsson Fredrik,Esbjörnsson Joakim,Biague Antonio,Medstrand Patrik,Norrgren Hans,Karlsson Annika C.,Jansson Marianne,
Abstract
HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DRint/high), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1high, TIGIThigh) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.
Funder
Vetenskapsrådet
Karolinska Institutet
Danmarks Frie Forskningsfond
Subject
Immunology,Immunology and Allergy
Reference77 articles.
1. HIV Interaction With Human Host: HIV-2 As a Model of a Less Virulent Infection;Azevedo-Pereira;AIDS Rev,2016
2. Baseline Plasma Viral Load and CD4 Cell Percentage Predict Survival in HIV-1- and HIV-2-Infected Women in a Community-Based Cohort in The Gambia;Hansmann;J Acquir Immune Defic Syndr,2005
3. Long-Term Follow-Up of HIV-2-Related AIDS and Mortality in Guinea-Bissau: A Prospective Open Cohort Study;Esbjornsson;Lancet HIV,2018
4. The Mortality and Pathology of HIV Infection in a West African City;Lucas;AIDS (London England),1993
5. Differences in Proviral DNA Load Between HIV-1- and HIV-2-Infected Patients;Gueudin;AIDS (London England),2008
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献