Prevention of oral tolerance induction to ovalbumin and enhanced antigen presentation during a graft-versus-host reaction in mice.

Systemic hyporesponsiveness after ingestion of a protein antigen (oral tolerance) depends on antigen processing by the gut and the actions of immunoregulatory T cells. We have examined the effects of a graft-versus-host reaction (GvHR) on oral tolerance, since both immune status and intestinal function are altered in GvHR. The GvHR was induced in unirradiated (CBA X BALB/c)F1 mice by intraperitoneal injection of CBA spleen cells. The tolerance of systemic humoral immunity and of delayed-type hypersensitivity normally found in mice fed 25 mg ovalbumin (OVA) was partially abrogated from 1 to 3 weeks after induction of the GvHR. In addition, mice with GvHR had a persistent enhancement of systemic immunity to OVA, and this was associated with an augmented ability of spleen cells to present OVA to primed T cells. The phagocytic activity of the reticuloendothelial system, as established by carbon clearance tests, was not altered by the GvHR. These findings suggest that enhanced antigen-presenting cell activity interferes with the induction of oral tolerance, and may be another pathogenetic mechanism of intestinal hypersensitivity disease.