Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals

Objectives: Lymphoid tissue is a major reservoir for virus replication in H IV-infected subjects. The relationship of CCR5 and CXCR4 coreceptor density and HIV replication in peripheral blood mononuclear cells (PBMC) and lymph node (LN) mononuclear cells (LNMC) of HIV-infected subjects was examined. Methods: PBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and eel lu lar viral load, coreceptor usage and CD38/HL A-DR expression. Results: The number of CCR5 and CXCR4 molecules on CD4 lymphocytes in the L N were significantly higher than in PBMC. In contrast the number of CD4 mol ecules/ CD4 T cell was higher in PBMC than in LNMC. The CXCR4/CD4 and CCR5/ CD4 ratios in the LN were significantly higher than in the PBMC. This was a ssociated with a cellular viral load in the LN that was similar to 110-fold higher than in PBMC. The absolute number of coreceptor molecules per cell did not correlate with the viral load. However, the CCR5/CD4 and CXCR4/CD4 ratios in the LN positively correlated with HIV cellular and plasma RNA. Ch aracterization of the viral isolates suggested an association between clini cal isolates using a distinct coreceptor and the upregulation of the corres ponding chemokine receptor. Conclusions: The ratios of chemokine receptors to CD4 molecules in CD4 T ce lls from LN is higher than in PBMC and may account for the relative differe nce in cellular viral load in these compartments. Additionally, the corecep tor/CD4 ratios, particularly in the lymphoid tissue, were highly related to HIV replication. (C) 2001 Lippincott Williams & Wilkins.