Abstract
The aim of this study was to assess whether interleukin-10 (IL-10) and/or transforming growth factor beta-1 (TGFbeta1) downregulate HLA-DR expression using the HT29 cell line as a model of colonic epithelial cells. HLA-DR expression was induced in HT29 cells with gamma-interferon. The effects of IL-10 alone, TGFbeta1 alone, and IL-10 and TGFbeta1 in combination were studied. HLA-DR expression was assessed using flow cytometric analysis. Gamma-interferon induced HLA-DR expression in a dose-dependent fashion. In the absence of gamma-interferon, neither IL-10 nor TGFbeta1 induced HLA-DR expression. In isolation, neither IL-10 nor TGFbeta1 downregulated HLA-DR expression. When IL-10 and TGFbeta1 were added in combination, small (6-30%) statistically significant reductions in HLA-DR expression were seen. The biological significance is unclear.
Highlights
HLA-DR molecules are cell surface heterodimers that act as immune recognition molecules
HLA-DR molecules are not expressed by colonic epithelium,[4] colonic epithelial cell expression of HLA-DR is seen in a variety of inflammatory bowel diseases.[5,6]
On the basis of these results, neither transforming growth factor b (TGFb) 1 nor IL-10 acting in isolation downregulate g -interferon-induced expression of HLA-DR within this experimental system
Summary
HLA-DR molecules are cell surface heterodimers that act as immune recognition molecules. A variety of antigen-presenting-cells present antigen in association with HLA-DR to lymphocytes. This interaction leads to lymphocyte activation and proliferation, and promotes inflammatory responses.[1] In addition to constitutive expression on a variety of cell types including lymphocytes, macrophages, vascular endothelium and some epithelial cells,[2] expression of HLADR molecules is induced in a much w ider range of cell types in the presence of inflammation.[3]. HLA-DR molecules are not expressed by colonic epithelium,[4] colonic epithelial cell expression of HLA-DR is seen in a variety of inflammatory bowel diseases.[5,6] In vitro studies have show n that HLA-DR-bearing colonic epithelial cells can present antigen to mucosal lymphocytes.[7,8] It is likely that HLA-DR expression by colonic epithelial cells is an important step in the generation of mucosal immune responses
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