HIV-1 infection and the lack of viral control are associated with greater expression of interleukin-21 receptor on CD8+ T cells

Autor: Jill Gilmour, Jama Dalel, Iavi Protocol C investigators list, Seng K Ung, Julia Makinde, Deborah King, S. Lucas Black, Sarah B. Joseph, Peter Hayes
Rok vydání: 2021
Předmět:
0301 basic medicine
Human immunodeficiency virus (HIV)
HIV Infections
CD360+
DETERMINANTS
CD8-Positive T-Lymphocytes
medicine.disease_cause
CD127 EXPRESSION
0302 clinical medicine
Basic Science
Immunology and Allergy
Cytotoxic T cell
IL-7R-ALPHA EXPRESSION
030212 general & internal medicine
Receptor
CD127+
11 Medical and Health Sciences
Effector
Interleukin-21 Receptor alpha Subunit
EXPANSION
Viral Load
17 Psychology and Cognitive Sciences
Peripheral
Infectious Diseases
Interleukin-21 receptor
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Receptors
Interleukin-21
EXHAUSTION
Life Sciences & Biomedicine
CD360(+)
Viral load
CD127(+)
Immunology
cytotoxic T lymphocytes
03 medical and health sciences
disease progression
Virology
interleukin-21 receptor
medicine
Humans
IAVI Protocol C investigators list
PROGRESSORS
Science & Technology
IL-7
interleukin-7 receptor
business.industry
06 Biological Sciences
GENE
030104 developmental biology
HIV-1
business
CD4(+)
CD8
RESPONSES
Zdroj: AIDS (London, England)
ISSN: 1473-5571
0269-9370
DOI: 10.1097/qad.0000000000002864
Popis: Supplemental Digital Content is available in the text
Objectives: Interleukin-21 (IL-21) has been linked with the generation of virus-specific memory CD8+ T cells following acute infection with HIV-1 and reduced exhaustion of CD8+ T cells. IL-21 has also been implicated in the promotion of CD8+ T-cell effector functions during viral infection. Little is known about the expression of interleukin-21 receptor (IL-21R) during HIV-1 infection or its role in HIV-1-specific CD8+ T-cell maintenance and subsequent viral control. Methods: We compared levels of IL-21R expression on total and memory subsets of CD8+ T cells from HIV-1-negative and HIV-1-positive donors. We also measured IL-21R on antigen-specific CD8+ T cells in volunteers who were positive for HIV-1 and had cytomegalovirus-responding T cells. Finally, we quantified plasma IL-21 in treatment-naive HIV-1-positive individuals and compared this with IL-21R expression. Results: IL-21R expression was significantly higher on CD8+ T cells (P = 0.0256), and on central memory (P = 0.0055) and effector memory (P = 0.0487) CD8+ T-cell subsets from HIV-1-positive individuals relative to HIV-1-negative individuals. For those infected with HIV-1, the levels of IL-21R expression on HIV-1-specific CD8+ T cells correlated significantly with visit viral load (r = 0.6667, P = 0.0152, n = 13) and inversely correlated with plasma IL-21 (r = −0.6273, P = 0.0440, n = 11). Lastly, CD8+ T cells from individuals with lower set point viral load who demonstrated better viral control had the lowest levels of IL-21R expression and highest levels of plasma IL-21. Conclusion: Our data demonstrates significant associations between IL-21R expression on peripheral CD8+ T cells and viral load, as well as disease trajectory. This suggests that the IL-21 receptor could be a novel marker of CD8+ T-cell dysfunction during HIV-1 infection.
Databáze: OpenAIRE
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