Inhibitory activity of intestinal intraepithelial lymphocytes.

Abstract

Intestinal intraepithelial lymphocytes (iIEL) are the first line of lymphoid cells exposed to orally absorbed foreign antigen. Because of this unique position, we hypothesized that the iIEL down-regulates the immune response to foreign antigen to prevent broad sensitization. One-way mixed lymphocyte cultures (MLCs) were performed with Brown Norway (BN) as the responder and irradiated Lewis rats as the stimulator. BN iIEL or control cells (irradiated BN spleen-thymus cells) were added to the MLCs to assess their inhibitory function. When iIEL cells comprised 0.63% of well volumes, a significant (p < 0.05) decline in MLC proliferation was seen. To determine whether this inhibitory action was mediated by a soluble factor, supernatant from iIEL cultured with irradiated Lewis spleen-thymus cells was added to MLCs and was compared with the addition of culture medium as the control group. The iIEL group proliferated significantly less (p < 0.05) than the control group. To further define the mechanism of action, iIEL-conditioned supernatant was treated with neutralizing antibody to transforming growth factor-beta (25 micrograms/ml) or control immunoglobulin. Treated supernatant was then added to an MLC, resulting in a partial loss of inhibitory action. The iIEL appears to significantly suppress a response to allogeneic stimuli via a mechanism mediated by the action of one or more soluble factors. Transforming growth factor-beta may well be one of the mediators of this inhibitory action.