Anti-alpha beta T cell receptor antibody prevents the progression of experimental autoimmune myocarditis.
We investigated the effects of anti-alpha beta T cell receptor antibody in rat experimental autoimmune myocarditis (EAM), using a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM.
Hanawa
H
H
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
Kodama
M
M
Inomata
T
T
Izumi
T
T
Shibata
A
A
Tuchida
M
M
Matsumoto
Y
Y
Abo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001835:Body Weight; D004195:Disease Models, Animal; D008297:Male; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta