Intestinal intraepithelial lymphocytes have a promiscuous interleukin-8 receptor.

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 alpha-chemokines, IL-8 and GRO, and the beta-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 beta 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 alpha and beta families, and this is likely to occur by the binding of the chemokines to common receptors.

Interleukin-7 activates intestinal lymphocytes.

Human intestinal lymphocytes, particularly intraepithelial lymphocytes, proliferate minimally to some agents, like mitogens and stimuli of the CD3 pathway. This in vitro finding may be due, in part, to a loss of factors found in vivo. Three T-cell growth factors, IL-7, IL-9, and IL-12, were tested for their ability to stimulate the proliferation of intestinal lymphocytes. Both intraepithelial lymphocytes and lamina propria lymphocytes proliferated more vigorously to IL-7 than to IL-9 or IL-12, and only IL-7 increased stimulation through the CD3 pathway. The IL-7-induced response was IL-2-dependent: IL-2 receptors appeared on both intestinal lymphocyte types, and antibody to the IL-2 receptor blocked IL-7-induced proliferation. Both CD4+ and CD8+ T-cell subsets responded to this cytokine as shown by phenotype-depletion experiments and constancy in the CD4/CD8 ratios after culture with IL-7. In addition, the T-cell receptor alpha beta and gamma delta subsets responded equally well to IL-7. This newly described selective proliferative response of intestinal lymphocytes to IL-7, but not to IL-9 or IL-12, requires no preactivation and may enhance growth in vivo.