Regulation of major histocompatibility complex class II synthesis by interleukin‐10

Summary 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.