1. Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection.
- Author
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Huang J, Al-Mozaini M, Rogich J, Carrington MF, Seiss K, Pereyra F, Lichterfeld M, and Yu XG
- Subjects
- Antigen Presentation drug effects, Blotting, Western, Gene Expression Profiling, Histocompatibility Antigens Class I biosynthesis, Histocompatibility Antigens Class I blood, Humans, Dendritic Cells immunology, HIV Infections immunology, HIV-1 immunology, HIV-1 pathogenicity, Histocompatibility Antigens Class I immunology, Immune Tolerance
- Abstract
Background: HIV-1 infection is associated with profound dysfunction of myeloid dendritic cells, for reasons that remain ill-defined. Soluble HLA class I molecules can have important inhibitory effects on T cells and NK cells, but may also contribute to reduced functional properties of professional antigen-presenting cells. Here, we investigated the expression of soluble HLA class I isoforms during HIV-1 infection and assessed their functional impact on antigen-presenting characteristics of dendritic cells., Results: Soluble HLA class I molecules were highly upregulated in progressive HIV-1 infection as determined by quantitative Western blots. This was associated with strong increases of intracellular expression of HLA class I isoforms in dendritic cells and monocytes. Using mixed lymphocyte reactions, we found that soluble HLA class I molecules effectively inhibited the antigen-presenting properties of dendritic cells, however, there was no significant influence of HLA class I molecules on the cytokine-secretion properties of these cells. The immunomodulatory effects of soluble HLA class I molecules were mediated by interactions with inhibitory myelomonocytic MHC class I receptors from the Leukocyte Immunoglobulin Like Receptor (LILR) family., Conclusions: During progressive HIV-1 infection, soluble HLA class I molecules can contribute to systemic immune dysfunction by inhibiting the antigen-presenting properties of myeloid dendritic cells through interactions with inhibitory myelomonocytic HLA class I receptors.
- Published
- 2012
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