Human intraepithelial lymphocytes

This study evaluates the immunomodulation and receptor binding of vasoactive intestinal peptide on human peripheral blood lymphocytes and intraepithelial lymphocytes. Vasoactive intestinal peptide (VIP, 10^–8 and 10^–12 M) had no effect on the concanavalin A-induced proliferation or the spontaneous cytotoxicity against K-562 targets by either lymphocyte type. Human peripheral blood lymphocytes had a mean of 927 vasoactive intestinal peptide receptors per cell with a K_d of 1.12×10^–10 M, as demonstrated by the competitive displacement of ¹²⁵I]peptide by unlabeled peptide using Scatchard analysis. In contrast, intraepithelial lymphocytes had no high-affinity receptors as shown by the negligible binding of 50 pM ¹²⁵I]VIP. Peptide binding by peripheral blood lymphocytes, although reduced by exposure to dithiothreitol and ethylenediamine tetraacetic acid, was still greater than binding by intraepithelial lymphocytes. As intraepithelial lymphocytes are mainly CD8⁺ T cells, the possibility that this phenotype may not bind VIP at all was tested by specifically depleting peripheral blood lymphocytes by antibody and complement lysis. Peripheral blood lymphocytes expressing CD8, CD4, and/or CD2 were responsible for most of the binding, indicating that CD8⁺ T lymphocytes in the peripheral blood and in the intestinal epithelium differ in their capacity to bind VIP.This work was supported by grants from the National Foundation for Ileitis and Colitis and from the National Institutes of Health (RO1DK42166).