Impaired class II expression and antigen uptake in monocytic cells after HIV-1 infection

Steven Polyak, Houchu Chen, David Hirsch, Italas George, Robert Hershberg, Kirk Sperber

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

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 colocalizalion 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 immu-nosuppression observed in AIDS.

Original languageEnglish
Pages (from-to)2177-2188
Number of pages12
JournalJournal of Immunology
Volume159
Issue number5
StatePublished - 1997
Externally publishedYes

Fingerprint

Dive into the research topics of 'Impaired class II expression and antigen uptake in monocytic cells after HIV-1 infection'. Together they form a unique fingerprint.

Cite this