CCR5 and CXCR4 Expression on Memory and Naive T Cells in HIV-1 Infection and Response to Highly Active Antiretroviral Therapy
作者:
Janet Nicholson,
Sandra Browning,
Richard Hengel,
Edward Lew,
Laura Gallagher,
David Rimland,
J. McDougal,
期刊:
JAIDS Journal of Acquired Immune Deficiency Syndromes
(OVID Available online 2001)
卷期:
Volume 27,
issue 2
页码: 105-115
ISSN:1525-4135
年代: 2001
出版商: OVID
关键词: Chemokine receptor;CCR5;CXCR4;T cells;HIV-1;Immune activation
数据来源: OVID
摘要:
ObjectiveTo measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets, measures of disease activity, and response to highly active antiretroviral therapy (HAART).DesignFourteen untreated HIV-1–infected patients, 18 patients at 3-to 4-weeks after beginning HAART, and 35 uninfected control subjects were studied.MethodsFour-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure their expression of CCR5, CXCR4, and CD38.ResultsHIV-1–infected patients had higher CCR5 levels and lower CXCR4 levels on CD4 and CD8 T cells and their CD45RO/CD45RA subsets than control subjects did. However, CCR5 elevation was statistically significant only for CD4 T cells and their subsets, and CXCR4 depression was significant for CD8 T cells and their subsets (and for CD4:CD45RO cells). The elevation of CCR5 and depression of CXCR4 were not due to shifts in CD45RO/CD45RA subset proportions but to upregulation or downregulation within the subsets. CCR5 elevation on CD4 T cells was significantly restored toward normal by HAART, but the CXCR4 depression was not. CCR5 expression but not CXCR4 expression correlated with other measures of immunodeficiency (CD4 T-cell levels), active infection (viral load), and cellular activation (CD38).ConclusionsCCR5 elevation is a concomitant of immune activation and viral replication that occurs in HIV-1 infection, but the relation of CXCR4 depression to severity of infection, disease progression, and response to therapy remains undefined.
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