7th Conference - Abstract 839

Enhanced CCR5 and CXCR4 Expression on Naive CD4+ T Cells from HIV-1-Infected Subjects

X. -D. LI*, L. MANGLE-ARNOLD, J. NICHOLS, J. NILES, R. POLLARD, and M. NOKTA. Univ. of Texas Med. Branch, Galveston

Chemokine receptors CCR5 and CXCR4 are the major co-receptors for HIV-1 infection of CD4⁺ T cells. In healthy HIV-1 negative donors, memory and naïve CD4⁺ T cells exhibit distinct expression patterns of these co-receptors. Several studies indicated that CCR5 is almost exclusively expressed on memory CD4⁺ T cells, while both memory and naïve CD4⁺ T cells express CXCR4. It has been previously shown that T-cell activation is essential for productive HIV-1 replication in CD4⁺ T cells and that HIV-1 infection preferentially occurred in memory CD4⁺ T cells. However, recent studies indicated that both memory and naïve CD4⁺ T cells from HIV⁺ subjects were infected. In this report, the cell surface expression of CCR5 and CXCR4 on CD4⁺/ICD45RO⁺ (memory) and CD4⁺/CD45RA⁺ (predominantly naïve) T cells was examined in 14 HIV-1 infected subjects. All subjects were naïve to anti-retroviral therapy. Six subjects had CD4 T cell count >400/mm³ (group I) and 8 had <400/mm³ group II). The median plasma viral load was 1,277 copies/ml (range: 50–7,835) and 45,168 copies/ml (123~510,842) for group I and group II subjects, respectively. Eight HIV-1 seronegative subjects were included as controls. The percentage of CCR5⁺ or CXCR4⁺ cells was measured on CD4⁺/CD45RO⁺ or CD4⁺/CD45RA⁺ cells as well as total CD4⁺ T cells by 3-color flow cytometry. Expression of CCR5 on naïve CD4⁺ T cells was significantly increased in group II (11.3 ± 3.3%) as compared to group I (2.7 ± 0.7%, p = 0.03) or the control (1.1 ± 0.9%, p = 0.017) subjects. The level of CXCR4 expression on naïve CD4⁺ T cells (2.6 ± 6.8%) was also significantly increased only in group II subjects as compared to the controls (3.8 ± 1.0%, p = 0.027), but was not statistically different from that in group I subjects (12.0 ± 3.3%). In contrast, levels of CCR5 expression on memory CD4⁺ cells were similar for the controls and group I and II subjects (31.8 ± 3.1%, 23.3 ± 4.1% and 37.9 ± 3.5%, respectively). A trend for an increase in the percentage of CXCR⁺memory CD4⁺ T cells was observed in groups I and II (10.0 ± 2.5% and 12.9 ± 3.1%) in comparison to the controls (5.6 ± l.%); however, the differences did not achieve statistical significance. These results suggest that, during HIV-1 infection, naïve CD4⁺ T cells exhibit increased expression of the major viral co-receptors, especially in subjects with more advanced infection. It is likely that the enhanced co-receptor expression on the naïve CD4⁺ T cells contributes to the permissiveness of the cells to infection and disease progression.

Key Words: CCR5 and CXCR4, HIV-1 infection, naive CD4 T cells