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HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype
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HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype
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Journal Article
HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype
2007
Overview
Some rare HIV-1-infected individuals, referred to as HIV controllers (HIC), have persistently undetectable plasma viral load in the absence of therapy. This control of HIV-1 replication has been associated with a strong, multifunctional specific CD8⁺ T cell response. However, no direct link between this immune response and the control of viremia has so far been provided. We investigated parameters of specific CD8⁺ T cell response and in vitro susceptibility to HIV-1 infection in 11 HIC. We found high frequencies of HIV-specific CD8⁺ T cells. Interestingly, these cells expressed the activation marker HLA-DR but not CD38. This unique phenotype differentiates HIV-specific CD8⁺ T cells from HIC and noncontroller subjects and likely reflects a high potential to expand upon exposure to antigen and a capacity to exert effector functions. Accordingly, although CD4⁺ T cells from HIC were fully susceptible to HIV-1 superinfection, their CD8⁺ T cells effectively suppressed HIV-1 infection. Remarkably, this potent anti-HIV activity was observed without prior stimulation of CD8⁺ T cells. This activity was not mediated by secreted inhibitory factors but was due to the elimination of infected CD4⁺ T cells and was observed only with autologous CD4⁺ T cells, indicating an HLA-restricted cytotoxic mechanism. This constitutive antiviral capacity of CD8⁺ T cells could account for the control of viral replication in HIC.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Aged
/ AIDS
/ antigens
/ Antiretroviral Therapy, Highly Active
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - pathology
/ CD4-Positive T-Lymphocytes - virology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - pathology
/ Female
/ Genetics
/ Highly active antiretroviral therapy
/ HIV
/ HIV 1
/ HIV Infections - drug therapy
/ HIV Infections - prevention & control
/ Human immunodeficiency virus
/ Human immunodeficiency virus 1
/ Humans
/ Lymphocyte Activation - drug effects
/ Lymphocyte Activation - immunology
/ Male
/ RNA
/ T-Lymphocytes, Cytotoxic - immunology
/ T-Lymphocytes, Cytotoxic - pathology
/ viremia
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