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CCR5 and CXCR4 Expression on Memory and Naive T Cells in HIV-1 Infection and Response to Highly Active Antiretroviral Therapy

2001; Lippincott Williams & Wilkins; Volume: 27; Issue: 2 Linguagem: Inglês

10.1097/00126334-200106010-00002

1944-7884

Janet K.A. Nicholson, Sandra W. Browning, Richard L. Hengel, Edward Lew, Laura E. Gallagher, David Rimland, J. Steven McDougal,

Chemokine receptors and signaling

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.