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Regulation of Autoreactive T Cell Function by Oral Tolerance to Self‐Antigens

Abstract: The oral administration of neuroantigens can suppress as well as treat autoimmune disease. Using EAE as a model system, we examined the antigen‐presenting cell in oral tolerance. Expansion of dendritic cells (DCs) prior to or after disease is established facilitated oral tolerance. Transfer of oral antigen‐loaded DCs resulted in protection from EAE by induction of IL‐4 and IL‐5 in recipient animals. LPS treatment of donors abrogated the ability of DCs to transfer protection from EAE, emphasizing the importance of the DC activation state. T cells exposed to orally administered antigen were monitored in TCR transgenic mice and found to undergo activation followed by deletion. The thymus plays a critical role in oral tolerance since thymectomized mice could not be tolerized. The thymus is postulated to be a site for deletion of autoreactive T cells or a site for generation of regulatory T cells.