Human intestinal intraepithelial lymphocytes have potent chemotactic activity.

Abstract

Inflammation is created by the movement of leukocytes toward soluble attractants (chemokines). The aim of this study was to identify the chemokines that attract intestinal lymphocytes. Intraepithelial and lamina propria lymphocytes were isolated from human jejunal mucosa of healthy individuals and cultured in interleukin (IL) 2 for 3 days. Migration was assessed using the Boyden transwell assay. Increases in cytoplasmic calcium ion concentration ([Ca2+]i) were measured from changes in fluorescence in Fura-2-loaded lymphocytes on exposure to the cytokines. A large number of intraepithelial lymphocytes migrated toward IL-8 and RANTES (regulated on activation, normal T cell expressed and secreted), and a small number migrated toward IL-10. In contrast, only a few lamina propria lymphocytes migrated toward IL-8, and none responded to the other chemokines tested. The chemokines IL-8 and IL-10, but not RANTES, increased [Ca2+]i in intraepithelial lymphocytes; this calcium mobilization was not affected by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, indicating that calcium is released from intracellular sources. None of the factors caused calcium mobilization by lamina propria lymphocytes. This study shows that intraepithelial lymphocytes have greater migratory and calcium-mobilizing activity than lamina propria lymphocytes and that these two activities do not correlate with each other.