EXPRESSION AND FUNCTION OF CCR5 AND CXCR4 ON HUMAN LANGERHANS CELLS AND MACROPHAGES - IMPLICATIONS FOR HIV PRIMARY INFECTION

Transmission of HIV-1 is predominantly restricted to macrophage (M Phi )-tropic strains. Langerhans cells (LCs) in mucosal epithelium, as wel l as macrophages located in the submucosal tissues, may be initial tar gets for HIV-1. This study was designed to determine whether restricte d transmission of HIV-1 correlates with expression and function of HIV -1 co-receptors on LCs and macrophages. Using polyclonal rabbit IgGs s pecific for the HIV co-receptors cytokines CXCR4 and CCR5, we found th at freshly isolated epidermal LCs (resembling resident mucosal LCs) ex pressed CCR5, but not CXCR, on their surfaces. In concordance with sur face expression, fresh LCs fused with M Phi-tropic but not with T-trop ic HIV-1 envelopes. However, fresh LCs did contain intracellular CXCR4 protein that was transported to the surface during in vitro culture. Macrophages expressed high levels of both co-receptors on their surfac es, but only CCR5 was functional in a fusion assay. These data provide several possible explanations for the selective transmission of M Phi -tropic HIV variants and for the resistance to infection conferred by the CCR5 deletion.