Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether r...

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Veröffentlicht in:PloS one Jg. 10; H. 10; S. e0139573
Hauptverfasser: Jensen, Sanne Skov, Fomsgaard, Anders, Larsen, Tine Kochendorf, Tingstedt, Jeanette Linnea, Gerstoft, Jan, Kronborg, Gitte, Pedersen, Court, Karlsson, Ingrid
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 01.10.2015
Public Library of Science (PLoS)
Schlagworte:
Adult
Aged
Anti-HIV Agents - therapeutic use
Antigens
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Antiretroviral Therapy, Highly Active
Case-Control Studies
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell activation
Cytometry
Drug therapy
Female
Flow cytometry
HIV
HIV Infections - drug therapy
HIV Infections - immunology
HIV Infections - virology
HIV-1 - drug effects
HIV-1 - immunology
Hospitals
Human immunodeficiency virus
Humans
Immune reconstitution
Immunity
Immunology
Infections
Infectious diseases
Interleukin 2
Laboratories
Life assessment
Lymphocytes
Lymphocytes T
Male
Markers
Middle Aged
PD-1 protein
Phenotypes
R&D
Research & development
Restoration
Seroconversion
Studies
T cell receptors
Therapy
Tumor necrosis factor-α
Viral infections
Viral Load - immunology
Virology
γ-Interferon
Denmark
ISSN:1932-6203, 1932-6203
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Zusammenfassung:CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: SSJ IK AF GK JG TKL JLT CP. Performed the experiments: SSJ IK AF GK JG TKL JLT CP. Analyzed the data: SSJ. Contributed reagents/materials/analysis tools: SSJ IK AF. Wrote the paper: SSJ IK.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0139573