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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

Author:
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
Source:
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.16 pp. 6776-6781
ISSN:
0027-8424
Subject:
CD4-positive T-lymphocytes, CD8-positive T-lymphocytes, HIV infections, Human immunodeficiency virus 1, antigens, antiretroviral properties, cytotoxicity, immune response, lymphocyte proliferation, phenotype, superinfection, therapeutics, viral load, viremia, virus replication
Abstract:
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.
Agid:
2352369