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High-level HIV-1 viremia suppresses viral antigen-specific CD4(+) T cell proliferation.

ABSTRACT: In chronic viral infections of humans and experimental animals, virus-specific CD4(+) T cell function is believed to be critical for induction and maintenance of host immunity that mediates effective restriction of viral replication. Because in vitro proliferation of HIV-specific memory CD4(+) T cells is only rarely demonstrable in HIV-infected individuals, it is presumed that HIV-specific CD4(+) T cells are killed upon encountering the virus, and maintenance of CD4(+) T cell responses in some patients causes the restriction of virus replication. In this study, proliferative responses were absent in patients with poorly restricted virus replication although HIV-specific CD4(+) T cells capable of producing IFN-gamma were detected. In a separate cohort, interruption of antiretroviral therapy resulted in the rapid and complete abrogation of virus-specific proliferation although HIV-1-specific CD4(+) T cells were present. HIV-specific proliferation returned when therapy was resumed and virus replication was controlled. Further, HIV-specific CD4(+) T cells of viremic patients could be induced to proliferate in response to HIV antigens when costimulation was provided by anti-CD28 antibody in vitro. Thus, HIV-1-specific CD4(+) T cells persist but remain poorly responsive (produce IFN-gamma but do not proliferate) in viremic patients. Unrestricted virus replication causes diminished proliferation of virus-specific CD4(+) T cells. Suppression of proliferation of HIV-specific CD4(+) T cells in the context of high levels of antigen may be a mechanism by which HIV or other persistently replicating viruses limit the precursor frequency of virus-specific CD4(+) T cells and disrupt the development of effective virus-specific immune responses.

SUBMITTER: McNeil AC

PROVIDER: S-EPMC61135 | biostudies-literature | 2001 Nov

REPOSITORIES: biostudies-literature

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High-level HIV-1 viremia suppresses viral antigen-specific CD4(+) T cell proliferation.

McNeil A C AC Shupert W L WL Iyasere C A CA Hallahan C W CW Mican J A JA Davey R T RT Connors M M

Proceedings of the National Academy of Sciences of the United States of America 20011101 24

In chronic viral infections of humans and experimental animals, virus-specific CD4(+) T cell function is believed to be critical for induction and maintenance of host immunity that mediates effective restriction of viral replication. Because in vitro proliferation of HIV-specific memory CD4(+) T cells is only rarely demonstrable in HIV-infected individuals, it is presumed that HIV-specific CD4(+) T cells are killed upon encountering the virus, and maintenance of CD4(+) T cell responses in some p ...[more]

PMID: 11717444

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Project description:CD8+ and CD4+ T cells from HIV infected patients with HIV-RNA viremia of >50 copies/ml and CD8+ and CD4+ T cells from healthy controls were isolated by negative selection (Miltenyi Biotech, Auburn, CA). Cell sorting of the CD4 and CD8 T cell subsets were performed based on surface staining of CD3+CD8+ or CD3+CD4+ and na ve CD45RA+CD27+CD127highHLA-DRlow, and CD3+CD8+ or CD3+CD4+ and memory CD45RA-CD27+CD127highHLA-DRlow. Sorted cell populations were spun down and stored as dry pellets at -80M-BM-0C. Samples analyzed by transcript levels of genes related to cytokine signaling were determined by the JAK/STAT Signaling Pathway microarray. CD8+ and CD4+ T cells from HIV infected patients with HIV-RNA viremia of >50 copies/ml and CD8+ and CD4+ T cells from healthy controls were isolated by negative selection (Miltenyi Biotech, Auburn, CA). Cell sorting of the CD4 and CD8 T cell subsets were performed based on surface staining of CD3+CD8+ or CD3+CD4+ and naM-CM-/ve CD45RA+CD27+CD127highHLA-DRlow, and CD3+CD8+ or CD3+CD4+ and memory CD45RA-CD27+CD127highHLA-DRlow. Sorted cell populations were spun down and stored as dry pellets at -80M-BM-0C. Samples analyzed by transcript levels of genes related to cytokine signaling were determined by the JAK/STAT Signaling Pathway microarray (http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-039A.html, SABiosciences Frederick, MD). Briefly, total RNA was harvested from each individual T cell subset from each patient or healthy control and contaminating DNA was digested with DNase. Messenger RNA was converted to cDNA and loaded onto PCR array plates for quantitative real-time PCR. Quantification of transcript levels was determined by normalizing to 5 housekeeping genes from each individual sample. Relative gene expression levels for each subset were averaged and compared between cell populations from the patient group and healthy controls. Because of the multiple comparisons only p values M-bM-^IM-$ 0.01 were considered significant.

Dataset Information

High-level HIV-1 viremia suppresses viral antigen-specific CD4(+) T cell proliferation.

Publications

High-level HIV-1 viremia suppresses viral antigen-specific CD4(+) T cell proliferation.

Similar Datasets

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