INHIBITION OF RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN SJL MICE BY FEEDING THE IMMUNODOMINANT PLP139-151 PEPTIDE

Peripheral antigen-specific tolerance can be induced by feeding protei n antigens. The mechanism has been described as either clonal anergy/d eletion or induction of antigen-specific regulatory cells that produce transforming growth factor-beta (TGF-beta). These two mechanisms have been linked to the magnitude and frequency of the dose of antigen fed ; a single high dose induces anergy/deletion, whereas multiple low dos es of antigen induce TGF-beta-secreting regulatory cells, In the prese nt study, we investigated the mechanisms of feeding soluble peptides o f proteolipid protein (PLP) for prevention of experimental autoimmune encephalomyelitis (EAE) induced by either intact PLP or the immunodomi nant PLP139-151 peptide, Feeding PLP139-151 prevented acute and relaps ing EAE induced tay either PLP139-151 or intact PLP, PLP139-151 feedin g induced anergy in the T helper 1 (Th1) population as measured by an inhibition of both proliferation and interferon-gamma (IFN-gamma) prod uction, Interleukin-4 (IL-4) production was Increased, but increased T GF-beta production was not observed, Importantly, PLP139-151 feeding i nduced anergy in peripheral and central nervous system (CNS)-infiltrat ing T cells, Feeding of the subdominant PLP epitope (PEP178-191) faile d to inhibit EAE induced by PLP139-151; therefore, oral tolerance was not due to induction of bystander suppression, These results demonstra te that both acute and relapsing paralysis in EAE can be prevented by feeding the immunodominant peptide of PLP. (C) 1996 Wiley Liss, Inc.