Lmb. Santos et al., ORAL TOLERANCE TO MYELIN BASIC-PROTEIN INDUCES REGULATORY TGF-BETA-SECRETING T-CELLS IN PEYERS-PATCHES OF SJL MICE, Cellular immunology, 157(2), 1994, pp. 439-447
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.