Intestinal intraepithelial lymphocytes have a promiscuous interleukin-8 receptor

Abstract

Background: Human intraepithelial lymphocytes (IELs), predominantly T cells of the CD8+CD45RO+ phenotype that are situated between epithelial cells, have a chemotactic response to the α-chemokines, IL-8 and GRO, and the β-chemokine, and the protein termed regulated on activation, normal T cell expressed and secreted (RANTES). Aim: To evaluate the specificity of the IL-8 receptor on IELs. Methods: Specificity was determined by the degree of desensitisation of the IL-8 response caused by each chemokine and the degree of inhibition of IL-8 binding to the cell. Results: IELs migrated towards two additional β chemokines, macrophage inflammatory protein-1 and monocyte chemotactic protein (MCP). All chemokines inhibited IL-8 induced chemotaxis and calcium ion mobilisation by IELs, with IL-8 having the greatest effect and MCP the least. In addition, specific binding of radiolabelled IL-8 to IELs was reduced by each of the five chemokines in cold competition experiments, whereas only GRO and IL-8 itself displaced 125I-IL-8 from receptors on peripheral blood mononuclear cells. Conclusions: The IL-8 responsiveness of IELs is desensitised by chemokines of both the α and β families, and this is likely to occur by the binding of the chemokines to common receptors.