title: Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection.
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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Huang
authors.forename: Maha
authors.initials: M
authors.lastname: Al-Mozaini
authors.forename: Jerome
authors.initials: J
authors.lastname: Rogich
authors.forename: Mary F
authors.initials: MF
authors.lastname: Carrington
authors.forename: Katherine
authors.initials: K
authors.lastname: Seiss
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance
chemical_list: D015395:Histocompatibility Antigens Class I