Induction of oral tolerance to cellular immune responses in the absence ofPeyer's patches

Systemic hyporesponsiveness occurs following oral administration of antigen (oral tolerance) and involves the uptake and processing of antigen by the gut-associated lymphoid tissue (GALT), which includes Peyer's patches (PP) lamina propria lymphocytes and mesenteric lymph nodes (MLN). Animals with t argeted mutations of genes in the tumor necrosis factor (TNF) family have d ifferential defects in the development of peripheral lymphoid organs includ ing PP and MLN, and provide a unique opportunity to investigate the role of GALT structures in the induction of oral tolerance. Oral tolerance could n ot be induced in TNF/lymphotoxin (LT) alpha-/- mice, which are devoid of bo th PP and MLN, although these animals could be tolerized by intraperitoneal administration of antigen, demonstrating the requirement for GALT for oral tolerance induction. LT beta-/- mice and LT alpha /LT beta+/- animals do n ot have PP but could be orally tolerized, as measured by IFN-gamma producti on and delayed-type hypersensitivity responses by administration of both lo w or high doses of ovalbumin. To further investigate the requirement for PP , we tested the progeny of LTP-receptor-IgG-fusion-protein (LT beta RigG)-t reated mice, which do not form PP but have an otherwise intact immune syste m. Although these animals had decreased fecal IgA production, they could be orally tolerized. Our results demonstrate that PP are not an absolute requ irement for the induction of either high- or low-dose oral tolerance, altho ugh oral tolerance could not be induced in animals devoid of both PP and ML N.