In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 83, No. 2 ( 1998-07-27), p. 133-140
Abstract:
Abstract —Experimental autoimmune myocarditis (EAM) resembles the giant cell myocarditis seen in humans, and recurrent forms lead to dilated cardiomyopathy. EAM has been shown to be a T cell–mediated autoimmune myocarditis. We have previously shown that cDNA encoding Vβ complementarity-determining region (CDR) 3 from heart– and pericardial space–infiltrating T cells in EAM induced by rod cardiac myosin contains more restricted sequences than that from normal spleen T cells. Recently, it has become apparent that several epitopes of EAM exist in rod cardiac myosin; therefore, T cells infiltrating into lesions may recognize certain epitopes in EAM induced by rod cardiac myosin. In this study, we examined heart– and pericardial space–infiltrating T-cell clonotypes in EAM induced by synthetic peptides of cardiac myosin. EAM was produced by immunization with synthetic peptides corresponding to N-terminally acetylated amino acids 1539 to 1555 of rat cardiac myosin α heavy chain. Five of 12 rats receiving synthetic peptides developed macroscopic signs of myocarditis. To examine T-cell receptor (TCR) Vβ expression and CDR3 of the TCR β chain of lesion-infiltrating T cells in EAM, total RNA was isolated from heart, pericardial effusion, spleen, lymph node, and peripheral blood. TCR Vβ expression of the T cells infiltrating the lesions revealed a predominance of Vβ4. On the basis of single-strand conformation polymorphism analysis for CDR3 of the TCR Vβ4 chain, heart– and pericardial space–infiltrating T cells were considered to be oligoclonal, whereas spleen, lymph node, and peripheral blood in a rat with EAM and spleen in a native rat were considered to be polyclonal. In the same rat, clonotypes of heart-infiltrating T cells were almost the same as those of pericardial space–infiltrating T cells. Furthermore, on sequence analysis for CDR3 of the TCR Vβ4 chain, the amino acid motifs were similar among T cells infiltrating into lesions of different EAM rats. In the present study, TCR β chains of heart– and pericardial space–infiltrating T cells in EAM induced by synthesized peptide consisting of 17 amino acids were examined. Vβ4+ T cells with similar Vβ CDR3 motifs that infiltrate the heart and pericardial space may recognize the same epitope.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.83.2.133
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1998
detail.hit.zdb_id:
1467838-X
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