Regulation of major histocompatibility complex class II synthesis by interleukin-10.
We have shown previously that interleukin-10 (IL-10) blocks the development and T-cell stimulatory capacity of human monocyte-derived dendritic cells, without apparently down-regulating the surface expression of co-stimulatory molecules or human leucocyte antigen (HLA) molecules. In the majority of donors (60%), the cell surface levels of HLA-DR actually increased upon IL-10 treatment. Here we have shown that IL-10 does not regulate HLA-DR transcription as assessed by polymerase chain reation. Epifluorescence microscopy analysis showed that IL-10 primarily increased the intracellular pool of HLA-DR. In fact, IL-10 directly increased HLA-DR protein synthesis. However, IL-10 did not significantly alter the synthesis of invariant chain (Ii), which plays a crucial role in the assembly, transport and loading of newly formed HLA class II molecules, nor the amount of Ii reaching the cell-surface. In contrast, IL-10 increased the amount of HLA-DR-bound Iip33 shortly after the HLA-DR complex assembly. We postulate that, upon IL-10 treatment, immature Ii-associated HLA II molecules can still transit to the cell surface as they do in immature dendritic cells and recycle to the intracellular space, where they accumulate. A higher proportion of Ii-associated HLA-DR, coupled to increased membrane recycling, may contribute to the lower T-cell stimulatory capacity of IL-10-treated dendritic cells.
Morel
Anne-Sophie
AS
The Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology and Medicine, Faculty of Medicine, London, UK.
Coulton
Gary
G
Londei
Marco
M
D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; C045084:invariant chain; D016753:Interleukin-10