ORAL TOLERANCE TO MYELIN BASIC-PROTEIN INDUCES REGULATORY TGF-BETA-SECRETING T-CELLS IN PEYERS-PATCHES OF SJL MICE

Oral administration of myelin basic protein (MBP) is an effective mean s of suppressing experimental autoimmune encephalomyelitis (EAE). In t he Lewis rat model, we have previously shown that this effect is media ted by active suppression as T lymphocytes from animals orally toleriz ed to MBP suppress in vitro immune responses and in vivo adoptively tr ansfer disease protection to naive recipients. This effect is mediated by the cytokine TGF-beta which is secreted by T cells from orally tol erized animals after being triggered by the oral tolerogen. In the pre sent study we investigated Peyer's patches in SJL mice following orall y administered MBP. Peyer's patches are one of the major lymphoid stru ctures of gut-associated lymphoid tissue, and a site thought to play a n important role in the induction of oral tolerance. Twenty-four hours after one feeding of 1 mg of MBP, there were no proliferative respons es to MBP in Peyer's patches. However, when Peyer's patches from MBP-f ed animals were stimulated with IL-2 in the presence of MBP, reduced p roliferation to IL-2 was observed, and this inhibition was reversed wi th anti-TGF-beta antibody. Suppression of IL-2-induced proliferation b y MBP was not observed in unfed animals or if Peyer's patches from MBP -fed animals were stimulated with a control antigen (ovalbumin). Stimu lation of Peyer's patches T cells from MBP-fed animals with MBP result ed in secretion of TGF-beta in a dose-related fashion with less TGF-be ta secretion at higher doses. Furthermore, cells from Peyer's patches of animals fed MBP adoptively transferred protection to actively induc ed EAE. Thus, MBP-specific TGF-beta-secreting regulatory cells recover ed from Peyer's patches after a single oral administration of MBP are not evident as measured by proliferation, but are capable of suppressi ng in vitro and in vivo cell-mediated immune responses. Peyer's patche s appear to be an important site for the induction of cells which medi ate the active suppression component of oral tolerance. (C) 1994 Acade mic Press, Inc.