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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

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.
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Contributor : Gianfranco Pancino <>
Submitted on : Monday, April 23, 2007 - 12:30:03 PM
Last modification on : Wednesday, September 16, 2020 - 5:04:42 PM
Long-term archiving on: : Wednesday, April 7, 2010 - 2:02:57 AM

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Asier Sáez-Cirión, Christine Lacabaratz, Olivier Lambotte, Pierre Versmisse, Alejandra Urrutia, et al.. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2007, 104 (16), pp.6776-6781. ⟨10.1073/pnas.0611244104⟩. ⟨pasteur-00142658⟩

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