Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals
(2021) In Frontiers in Immunology 12.- 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... (More)
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.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2021-10-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- aviremic, CD226, CD8 T cell phenotypes, costimulation, HIV-2, immune activation, T cell exhaustion, TIGIT
- in
- Frontiers in Immunology
- volume
- 12
- article number
- 744530
- publisher
- Frontiers Media S. A.
- external identifiers
-
- pmid:34712231
- scopus:85117899922
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2021.744530
- language
- English
- LU publication?
- yes
- id
- c9c387fb-7979-4f73-ab73-e5d757669d67
- date added to LUP
- 2022-10-13 08:55:28
- date last changed
- 2024-09-20 05:17:05
@article{c9c387fb-7979-4f73-ab73-e5d757669d67, abstract = {{<p>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-DR<sup>int/high</sup>), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1<sup>high</sup>, TIGIT<sup>high</sup>) 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.</p>}}, author = {{Scharf, Lydia and Pedersen, Christina B. and Johansson, Emil and Lindman, Jacob and Olsen, Lars R and Buggert, Marcus and Wilhelmson, Sten and Månsson, Fredrik and Esbjörnsson, Joakim and Biague, Antonio and Medstrand, Patrik and Norrgren, Hans and Karlsson, Annika C. and Jansson, Marianne}}, issn = {{1664-3224}}, keywords = {{aviremic; CD226; CD8 T cell phenotypes; costimulation; HIV-2; immune activation; T cell exhaustion; TIGIT}}, language = {{eng}}, month = {{10}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals}}, url = {{http://dx.doi.org/10.3389/fimmu.2021.744530}}, doi = {{10.3389/fimmu.2021.744530}}, volume = {{12}}, year = {{2021}}, }