HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 16; pp. 6776 - 6781
• Main Authors: Sáez-Cirión, Asier, Lacabaratz, Christine, Lambotte, Olivier, Versmisse, Pierre, Urrutia, Alejandra, Boufassa, Faroudy, Barré-Sinoussi, Françoise, Delfraissy, Jean-François, Sinet, Martine, Pancino, Gianfranco, Venet, Alain
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.04.2007; National Acad Sciences
• Subjects: Adult; Aged; AIDS; antigens; antiretroviral properties; Antiretroviral Therapy, Highly Active; Antivirals; Biological Sciences; Blood plasma; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Coculture techniques; cytotoxicity; Female; Genetics; Genotype & phenotype; Highly active antiretroviral therapy; HIV; HIV 1; HIV infections; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - pathology; HIV Infections - prevention & control; HIV-1 - immunology; Human health and pathology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immune response; Immunology; Immunophenotyping; Infections; Infectious diseases; Life Sciences; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; lymphocyte proliferation; Lymphocyte receptors; Lymphocytes; Male; Middle Aged; phenotype; RNA; superinfection; T cell receptors; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology; therapeutics; viral load; viremia; virus replication; Virus Replication - drug effects; Virus Replication - immunology; HIV suppression; "HLA-DR"; "HIV suppression"; CD8+ T cells; HLA-DR; CD38; "CD8+ T cells "; "CD38"
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0611244104

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.