IMPAIRED CLASS-II EXPRESSION AND ANTIGEN UPTAKE IN MONOCYTIC CELLS AFTER HIV-1 INFECTION

Using the human macrophage hybridoma cell line 43 and primary monocyte s, we investigated the regulation of class II expression and intracell ular Ag trafficking after HIV-1 infection. The HIV-1-infected human ma crophage hybridoma cell line, 43(HIV), lost class II Ag expression, as determined by immunofluorescence, immunoprecipitation, and Northern b lot analysis, 2 wk after infection, Class II expression could be resto red by transfection with the full-length HLA-DR4 cDNA driven by a CMV IE promotor. However, even after transfection, the 43(HIV) cells were incapable of presenting Ag to MHC-matched Ag-specific T cells, This de fect was associated with decreased formation of class II-Ag complexes, and similar findings were observed in primary HIV-1(BaL)-infected mon ocytes, We investigated Ag uptake using FITC-labeled tetanus, OVA, and keyhole limpet hemocyanin, There was decreased uptake of all three Ag s after HIV-1 infection at different time points after Ag pulsing in t he 43(HIV) cells and in primary HIV-1(BaL)-infected monocytes. There w as colocalization of the FITC-labeled Ags with early (cathepsin D) and late endosomal markers (anti-mannose-6-phosphate receptor), lysosomal markers (CD-63), and acidic compartment markers ,4-dinitroanilino)-3' -amino-N-methyldipropylamine) in the uninfected cells, but the level o f colocalized Ag was reduced in the 43(HIV) cells and HIV-1(BaL)-infec ted monocytes. Our data suggest that class II expression, formation of class II-Ag complexes, and Ag uptake are impaired in chronically HIV- 1-infected monocytic cells, which may contribute to the global immunos uppression observed in AIDS.