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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.

SUBMITTER: Saez-Cirion A 

PROVIDER: S-EPMC1851664 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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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.

Sáez-Cirión Asier A   Lacabaratz Christine C   Lambotte Olivier O   Versmisse Pierre P   Urrutia Alejandra A   Boufassa Faroudy F   Barré-Sinoussi Françoise F   Delfraissy Jean-François JF   Sinet Martine M   Pancino Gianfranco G   Venet Alain A  

Proceedings of the National Academy of Sciences of the United States of America 20070411 16


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 f  ...[more]

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