IMPAIRED MACROPHAGE FUNCTION AND ENHANCED T-CELL-DEPENDENT IMMUNE-RESPONSE IN MICE LACKING CCR5, THE MOUSE HOMOLOG OF THE MAJOR HIV-1 CORECEPTOR

The CC-chemokine receptor CCR5 has been shown to be the major corecept or for HIV-1 entry into cells, and humans with homozygous mutation in the ccr5 gene are highly resistant to HIV-1 infection, despite the exi stence of many other HIV-1 core ceptors, To investigate the physiologi c function of CCR5 and to understand the cellular mechanisms of these clinical observations, we generated a CCR5-deficient mouse model (ccr5 (-/-)) by targeted deletion of the ccr5 gene, We found that although d eveloped normally in a pathogen-free environment, CCR5-deficient mice showed reduced efficiency in clearance of Listeria infection and exser t a protective effect aganist LPS-induced endotoxemia, reflecting a pa rtial defect in macrophage function, In addition, CCR5-deficient mice had an enhanced delayed-type hypersensitivity reaction and increased h umoral responses to T cell-dependent antigenic challenge, indicating a novel role of CCR5 in down-modulating T cell-dependent immune respons e.