Human intestinal mucosa alters T-cell reactivities.

Abstract

Compared with T cells in peripheral blood, lamina propria T lymphocytes have a low proliferative response to stimulation via the T-cell antigen receptor/CD3 complex or by protein kinase C activators yet largely preserve or even show an enhanced reactivity to CD2 and CD28 triggering. Coculture of peripheral blood T lymphocytes with intestinal mucosa supernatant leads to a similar functional behavior as found in freshly recovered lamina propria T lymphocytes. The aim of this study is to characterize the nature of substances in the mucosal supernatant responsible for downregulation of T-cell receptor-dependent signals. Mucosal supernatant was produced, dialyzed, digested with proteinase K, reduced by 2-mercaptoethanol or dithiothreitol, and tested for its activity on peripheral blood T lymphocytes. Supernatant lost its activity after dialysis through a membrane (pore size 12,000-14,000). Digestion with proteinase K does not abolish its activity suggesting that the substances are neither proteins nor peptides. However, its effects on T lymphocyte proliferation can be reversed by reducing agents like 2-mercaptoethanol or dithiothreitol, suggesting that oxidative substances are contained in mucosal supernatants. Our data support the view that mucosal substances that down-regulate antigen receptor-induced T lymphocyte proliferation are small, nonprotein, nonpeptide molecules with oxidative properties.