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Published on: May 30, 2013
CCR5 and CXCR4 expression on memory and naive T cells in HIV-1 infection and response to highly active antiretroviral
J K Nicholson1, S W Browning, R L Hengel
1HIV Immunology and Diagnostics Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, U.S.A.
Objective:
To 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).
Design:
Fourteen untreated HIV-1-infected patients, 18 patients at 3-to 4-weeks after beginning HAART, and 35 uninfected control subjects were studied.
Methods:
Four-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.
Results:
HIV-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).
Conclusions:
CCR5 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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