CD4 but not CD8 T cells are required for the induction of oral tolerance

Abstract

It has been suggested that oral tolerance is mediated by CD8+ T lymphocytes, but the functional properties of these cells are unclear. Here we show that the induction of tolerance by feeding mice ovalbumin (OVA) does not prime antigen-specific class I MHC-restrlcted cytotoxic T cells In vivo. Indeed, such responses are markedly suppressed in mice fed OVA, and the induction of oral tolerance is abolished by depletion In vivo of CD4+ but not CD8+ T cells. These results indicate that CD8+ lymphocytes are unlikely to play a major role In the induction of oral tolerance and are the first demonstration that specific cytotoxic responses to an exogenous antigen can be suppressed by feeding antigen. The ability of orally administered protein antigens to induce tolerance has been proposed as a treatment for a variety of autoimmune diseases (1-4) and presents a major obstacle to the development of oral vaccines. Therefore it is important to determine the mechanisms underlying the phenomenon of oral tolerance