Antigen therapy eliminates T cell inflammation by apoptosis: effective treatment of experimental autoimmune neuritis with recombinant myelin protein P2.
Exposure of T cells to their specific antigen normally results in proliferation, but in the presence of high and repeatedly administered doses of antigen, T cells may undergo apoptosis. Here we demonstrate that i.v. administration of as little as 100 microg of recombinant P2 protein twice daily completely prevents experimental autoimmune neuritis induced by adoptive transfer of neuritogenic P2-specific T cells or by immunization with the neuritogenic P2-peptide-spanning amino acids 53-78. Antigen treatment started after disease onset markedly ameliorated experimental autoimmune neuritis. The mechanism of action may be through programmed T cell death; a profound increase of the rate of apoptosis was seen in inflammatory foci of peripheral nerves and in the spleen. There was no cytokine switch by our Th1 cells after exposure to their specific antigen, but increased secretion of interferon gamma and tumor necrosis factor alpha was demonstrated. High antigen dose therapy using recombinant, pathogen-free protein may prove useful for the treatment of autoimmune inflammatory disorders of the nervous system.
Weishaupt
A
A
Department of Neurology, Julius-Maximilians Universität, Würzburg, Germany.
Gold
R
R
Gaupp
S
S
Giegerich
G
G
Hartung
H P
HP
Toyka
K V
KV
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007114:Immunization; D007249:Inflammation / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000628:therapy*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D011994:Recombinant Proteins; C076290:myelin P2 peptide SP26