Abrogation of oral tolerance by contrasuppressor T cells suggests the presence of regulatory T-cell networks in the mucosal immune system

Abstract

Continuous ingestion of a thymus-dependent (TD) antigen differentially affects two compartments of the immune system. A secretory IgA antibody response is induced in mucosal tissues, concurrent with a state of antigen-specific systemic unresponsiveness to parenteral challenge¹, termed oral tolerance². The precise mechanisms whereby gut antigenic exposure induces oral tolerance are unknown, although T-suppressor cells^3,4, anti-idiotypic networks⁵ and immune complex formation⁶ have all been proposed. Here we show that the systemic unresponsiveness of mice made orally tolerant to the TD antigen sheep red blood cells (SRBC) is reversed by the adoptive transfer of Lyt-1⁺,2⁻, Vicia villosa lectin-adherent and I–J⁺ T cells derived from mice which are genetically resistant to the induction of oral tolerance to SRBC. This T-cell subpopulation has the characteristics of contrasuppressor effector T cells (T_cs). Small numbers of these T_cs cells reverse SRBC-specific tolerance both in vivo and in vitro. This finding offers new insight into the mechanisms of oral tolerance induction and maintenance, and suggests that a network of T cells are involved in the regulation of host responses to ingested antigens.