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 protein antigens. The mechanism has been described as either clonal anergy/deletion 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 doses of antigen induce TGF-beta-secreting regulatory cells. In the present study, we investigated the mechanisms of feeding soluble peptides of proteolipid protein (PLP) for prevention of experimental autoimmune encephalomyelitis (EAE) induced by either intact PLP or the immunodominant PLP139-151 peptide. Feeding PLP139-151 prevented acute and relapsing EAE induced by either PLP139-151 or intact PLP. PLP139-151 feeding induced anergy in the T helper 1 (Th1) population as measured by an inhibition of both proliferation and interferon-gamma (IFN-gamma) production. Interleukin-4 (IL-4) production was increased, but increased TGF-beta production was not observed. Importantly, PLP139-151 feeding induced anergy in peripheral and central nervous system (CNS)-in-filtrating T cells. Feeding of the subdominant PLP epitope (PLP178-191) failed to inhibit EAE induced by PLP139-151; therefore, oral tolerance was not due to induction of bystander suppression. These results demonstrate that both acute and relapsing paralysis in EAE can be prevented by feeding the immunodominant peptide of PLP.
Karpus
W J
WJ
Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, IL 60611, USA. w-karpus@nwu.edu
Kennedy
K J
KJ
Smith
W S
WS
Miller
S D
SD
D000284:Administration, Oral; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000276:immunology / Q000494:pharmacology*; D018991:Myelin Proteolipid Protein / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016056:Immunodominant Epitopes; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D015847:Interleukin-4