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HLA-G+ HIV-1-specific CD8+ T cells are associated with HIV-1 immune control.

ABSTRACT: To assess the frequency and function of HIV-1-specific HLA-G (histocompatibility antigen class I, G) CD8 T cells in HIV-1 controllers and progressors.We performed an observational cross-sectional cohort analysis in untreated (n?=?47) and treated (n?=?17) HIV-1 patients with different rates of disease progression and n?=?14 healthy individuals.We evaluated the frequency, the proportion and the function of total and virus-specific HLA-G CD8 T cells by tetramer or intracellular cytokine staining, followed by flow cytometric analysis. Cytokine secretion of sorted CD8 T-cell subsets was evaluated by Luminex assays.The proportion and the absolute frequency of HLA-G HIV-1-specific CD8 T cells were directly associated with CD4 T-cell counts and inversely correlated with viral loads, whereas total or HLA-G-negative HIV-1-specific CD8 T cells were not. In functional assays, HLA-G CD8 T cells from HIV-1-negative individuals had higher abilities to produce the antiviral (C-C chemokine receptor type 5) ligands MIP-1? (macrophage inflammatory protein-1ß), MIP-1? and Rantes.HLA-G HIV-1-specific CD8 T cells may represent a previously unrecognized correlate of HIV-1 immune control.

SUBMITTER: Vigano S

PROVIDER: S-EPMC5177477 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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HLA-G+ HIV-1-specific CD8+ T cells are associated with HIV-1 immune control.

Viganò Selena S Negrón Jordi J JJ Tse Samantha S Chowdhury Fatema Z FZ Lichterfeld Mathias M Yu Xu G XG

AIDS (London, England) 20170101 2

<h4>Objective(s)</h4>To assess the frequency and function of HIV-1-specific HLA-G (histocompatibility antigen class I, G) CD8 T cells in HIV-1 controllers and progressors.<h4>Design</h4>We performed an observational cross-sectional cohort analysis in untreated (n = 47) and treated (n = 17) HIV-1 patients with different rates of disease progression and n = 14 healthy individuals.<h4>Methods</h4>We evaluated the frequency, the proportion and the function of total and virus-specific HLA-G CD8 T cel ...[more]

PMID: 27835619

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Project description:UnlabelledCD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection.ImportanceThe ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology.

Dataset Information

HLA-G+ HIV-1-specific CD8+ T cells are associated with HIV-1 immune control.

Publications

HLA-G+ HIV-1-specific CD8+ T cells are associated with HIV-1 immune control.

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