Expression and function of chemokine receptors on human thymocytes: Implications for infection by human immunodeficiency virus type 1

The presence or absence of the receptor CD4 and the coreceptors CCR5 and CX CR4 restrict the cell tropism of human immunodeficiency virus type 1 (HIV-1 ). Despite the importance of thymic infection by HIV-1, conflicting reports regarding the expression of HIV-1 coreceptors on human thymocytes have not been resolved. We assayed the expression and function of the major HIV-1 c oreceptors, CCR5 and CXCR4, as well as CCR4 and CCR7 as controls, on human thymocytes. We detected CCR5 on 2.5% of thymocytes, CXCR4 on 53% of the cel ls, and CCR4 on 16% and CCR7 on 11% of human thymocytes. Moreover, infectio n by R5 HIV-1 did not significantly induce expression of CCR5. We found tha t two widely used anti-CCR5 monoclonal antibodies cross-reacted with CCR8, which may account for discrepancies among published reports of CCR5 express ion on primary cells. This cross-reactivity could be eliminated by deletion of amino acids 2 through 4 of CCR8. Chemotaxis assays showed that SDF-1, w hich binds CXCR4; MDC, which binds CCR4; and ELC, which binds CCR7, mediate d significant chemotaxis of thymocytes. In contrast, MIP-1 beta, whose rece ptor is CCR5, did not induce significant chemotaxis. Our results indicate t hat CXCR4, CCR4, CCR7, and their chemokine ligands may be involved in thymo cyte migration during development in the thymus. CCR5 and its ligands, howe ver, are likely not involved in these processes. Furthermore, the pattern o f CCR5 and CXCR4 expression that we found may explain the greater susceptib ility of human thymocytes to infection by HIV-1 isolates capable of using C XCR4 in cell entry compared to those that use only CCR5.