Difference in gut mucosal immunity in multiple sclerosis and myasthenia gravis and the safety in oral tolerance induction.

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This 2-year project aimed at establishing a 7-day culture system for peripheral blood mononuclear cells (PBMNC) which proliferate in response to dietary protein antigens such as ovalbumin (OVA), bovine serum albumin (BSA), kappa-casein (k-C), and bovine gamma-globulin (BGG). If a simple screening test for checking gut mucosal immunity, which under the normal condition renders induction of hyporesponsiveness in systemic immunity against an antigen taken up through the gut, becomes feasible among patients with multiple sclerosis (MS) and myasthenia gravis (MG), this approach would be of help to select patients who are the best candidates of a new treatment strategy, i.e., oral tolerance. The following results were obtained.1.The optimum concentrations of dietary antigens in culturing PBMNC were 50 and 100mg/ml. Tritium-labelled thymidine incorporation during the final 16 hours of a 7-day culture of PBMNC with dietary antigens was used as a measure of proliferative response to each antigen. With this method responses to OVA and BGG were found not only in patients with MS but also in those with MG and healthy controls. There was no response to BSA in the latter two groups, whereas high responsiveness to k-C may be representative of the gut mucosal immunity specific to MS.2.A proliferative response as measured by thymidine incorporation correlated with an expansion of CD4^+CD26^+ memory helper T cells after seven days of cell culture. In order to investigate the relationship between cytokine levels and aforementioned results, the culture supernatants for each antigen were stored at -70ﾟC.3.It was proved by using keyhole limpet hemocyanin (KLH) that measurement of precursor cell frequency specific with KLH against which human subjects were orally tolerized was the most sensitive method for monitoring induction of oral tolerance and gave reproducible results.