Huang, JingheAl-Mozaini, Maha AhmedRogich, JeromeCarrington, Mary F.Seiss, KatherinePereyra, FLichterfeld, MathiasYu, Xu2012-12-112012Huang, Jinghe, Maha Al-Mozaini, Jerome Rogich, Mary F. Carrington, Katherine Seiss, Florencia Pereyra, Mathias Lichterfeld, and Xu G. Yu. 2012. Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection. Retrovirology 9: 11.1742-4690http://nrs.harvard.edu/urn-3:HUL.InstRepos:10026705Background: 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.en-USimmunoregulationHLAdendritic cellsHIV-1leukocyte immunoglobulin-like receptorJournal Article2012-12-1110.1186/1742-4690-9-11