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Vaccination, prevention, and treatment of experimental autoimmune neuritis (EAN) by an oligomerized T cell epitope

Official URL:https://doi.org/10.1073/pnas.241504598
PubMed:View item in PubMed
Creators Name:Stienekemeier, M. and Falk, K. and Roetzschke, O. and Weishaupt, A. and Schneider, C. and Toyka, K.V. and Gold, R. and Strominger, J.L.
Journal Title:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation:Proc Natl Acad Sci U S A
Volume:98
Number:24
Page Range:13872-13877
Date:1 November 2001
Keywords:Apoptosis, Autoantigens, Cell Division, Cell Line, Down-Regulation, Experimental Autoimmune Neuritis, Inbred Lew Rats, Immunotherapy, Lymph Nodes, Myelin P2 Protein, Oligopeptides, Peptide Fragments, Solubility, Synthetic Vaccines, T-Lymphocyte Epitopes, T-Lymphocytes, Vaccination, Animals, Rats
Abstract:Using a polypeptide oligomer harboring 16 repeats of the neuritogenic epitope (aa 58-73) of myelin P2 protein separated by spacers, enhancement of the immune response to the P2 protein, an important neuritogenic autoantigen in experimental autoimmune neuritis (EAN), was attempted. In contrast to a previous study with PLP-16-mer antigen-specific response of T cells was attenuated at all doses examined to a variable degree. Treatment of Lewis rats with the P2-16-mer up to 2 months before immunization with P253-78 (vaccination) or after immunization but before appearance of disease (prevention) had a strong tolerizing effect against the induction of EAN on immunization with P253-78. Moreover, rats injected with 200 μg of the P2-16-mer i.v. on day 11 after disease induction, at which time the initial signs of disease had appeared, were almost completely protected against progression of clinical disease, whereas animals treated with the same amount of monomeric control peptide developed severe disease (treatment). Similar results were obtained by i.v. treatment of adoptive-transfer EAN with the P2-16-mer. The lack of clinical signs of disease after 16-mer therapy could be correlated with a reduced proliferative response of P253-78-specific lymph node cells. The frequency of apoptotic T cells in sciatic nerve or in lymph node cells, however, was not increased by the 16-mer treatment, suggesting that induction of anergy or other forms of peripheral tolerance may be responsible for the effect. Thus, the oligomerized P2 peptide antigen was highly effective in all three treatment modalities examined in this specific autoreactive T cell-mediated immune response.
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Item Type:Article

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