Impaired class II expression and antigen uptake in monocytic cells after HIV-1 infection.
Using the human macrophage hybridoma cell line 43 and primary monocytes, we investigated the regulation of class II expression and intracellular Ag trafficking after HIV-1 infection. The HIV-1-infected human macrophage hybridoma cell line, 43HIV, lost class II Ag expression, as determined by immunofluorescence, immunoprecipitation, and Northern blot analysis, 2 wk after infection. Class II expression could be restored by transfection with the full-length HLA-DR4 cDNA driven by a CMV IE promotor. However, even after transfection, the 43HIV cells were incapable of presenting Ag to MHC-matched Ag-specific T cells. This defect was associated with decreased formation of class II-Ag complexes, and similar findings were observed in primary HIV-1BaL-infected monocytes. We investigated Ag uptake using FITC-labeled tetanus, OVA, and keyhole limpet hemocyanin. There was decreased uptake of all three Ags after HIV-1 infection at different time points after Ag pulsing in the 43HIV cells and in primary HIV-1BaL-infected monocytes. There was 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 (3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine) in the uninfected cells, but the level of colocalized Ag was reduced in the 43HIV cells and HIV-1BaL-infected 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 immunosuppression observed in AIDS.
Polyak
S
S
Division of Clinical Immunology, Mount Sinai Medical Center, New York, NY 10029, USA.
Chen
H
H
Hirsch
D
D
George
I
I
Hershberg
R
R
Sperber
K
K
D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics; D004705:Endocytosis; D017781:Genes, Immediate-Early; D005814:Genes, Viral; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006433:Hemocyanins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D000941:Antigens; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin