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Inverted CD8 T-Cell...
Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals
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- Scharf, Lydia (författare)
- Karolinska Institute
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- Pedersen, Christina B. (författare)
- Copenhagen University Hospital,Technical University of Denmark
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- Johansson, Emil (författare)
- Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,HIV-1 och HIV-2 värd interaktioner,Forskargrupper vid Lunds universitet,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine,HIV-1 and HIV-2 host interactions,Lund University Research Groups
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- Lindman, Jacob (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Olsen, Lars R (författare)
- Copenhagen University Hospital,Technical University of Denmark
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- Buggert, Marcus (författare)
- Karolinska Institutet,Karolinska Institute
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- Wilhelmson, Sten (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk virologi, Malmö,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Virology, Malmö,Lund University Research Groups
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- Månsson, Fredrik (författare)
- Lund University,Lunds universitet,Klinisk infektionsmedicin,Forskargrupper vid Lunds universitet,Clinical infection medicine,Lund University Research Groups
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- Esbjörnsson, Joakim (författare)
- Lund University,Lunds universitet,Systemvirologi,Forskargrupper vid Lunds universitet,Systems Virology,Lund University Research Groups
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Biague, Antonio (författare)
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- Medstrand, Patrik (författare)
- Lund University,Lunds universitet,Klinisk virologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Virology, Malmö,Lund University Research Groups
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- Norrgren, Hans (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Karlsson, Annika C. (författare)
- Karolinska Institutet,Karolinska Institute
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- Jansson, Marianne (författare)
- Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,HIV-1 och HIV-2 värd interaktioner,Forskargrupper vid Lunds universitet,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine,HIV-1 and HIV-2 host interactions,Lund University Research Groups
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(creator_code:org_t)
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- 2021-10-12
- 2021
- Engelska.
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- aviremic
- CD226
- CD8 T cell phenotypes
- costimulation
- HIV-2
- immune activation
- T cell exhaustion
- TIGIT
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Scharf, Lydia
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Pedersen, Christ ...
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Johansson, Emil
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Lindman, Jacob
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Olsen, Lars R
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Buggert, Marcus
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visa fler...
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Wilhelmson, Sten
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Månsson, Fredrik
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Esbjörnsson, Joa ...
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Biague, Antonio
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Medstrand, Patri ...
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Norrgren, Hans
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Karlsson, Annika ...
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Jansson, Mariann ...
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Lunds universitet
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Karolinska Institutet