Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection

Retrovirology

Xu G Yu²  Mathias Lichterfeld³  Florencia Pereyra²  Katherine Seiss²  Mary F Carrington²  Jerome Rogich²  Maha Al-Mozaini¹  Jinghe Huang² 

[1] King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia;Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA;Infectious Disease Division, Massachusetts General Hospital, Boston, MA, USA

关键词: Leukocyte Immunoglobulin Like Receptor (LILR);    immunoregulation;    HLA;    dendritic cells;    HIV-1;   

Others  :  1209346
DOI  :  10.1186/1742-4690-9-11

 received in 2011-10-14, accepted in 2012-01-30,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Huang et al; licensee BioMed Central Ltd.

【 图 表 】

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