Analysis of TCR Vβ repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy

被引:84
作者
Luppi, P
Licata, A
Haluszczak, C
Rudert, WA
Trucco, G
McGowan, FX
Finegold, D
Boyle, GJ
Trucco, M
机构
[1] Childrens Hosp Pittsburgh, Rangos Res Ctr, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Pediat, Div Immunogenet, Pittsburgh, PA 15260 USA
[3] Univ Pittsburgh, Sch Med, Dept Pathol, Div Immunogenet, Pittsburgh, PA USA
[4] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA
[5] Childrens Hosp, Anesthesia Crit Care Med Labs, Boston, MA 02115 USA
[6] Univ Pittsburgh, Dept Pediat, Div Endocrinol, Pittsburgh, PA 15260 USA
[7] Univ Pittsburgh, Dept Pediat, Div Cardiol, Pittsburgh, PA 15260 USA
关键词
T cell receptor; cytokine; coxsackie virus B; cardiomyopathy; myocarditis;
D O I
10.1006/jaut.2000.0462
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 [免疫学];
摘要
Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3(+)-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-V beta) encoding families V beta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and presence of enterovirus-specific antigens. IDC patients who underwent heart transplantation at different times after the onset of heart failure were studied. A cardiac infiltrate of CD4(+) and CD8(+) T cells was present together with activated macrophages. Furthermore, the same V beta gene families, previously found to be skewed in hearts from fulminant cases of CVB3(+)-IDC, together with two additional V beta gene families, V beta1 and 5B, were increased. IL-1 beta, IL-2, IL-6 and IFN-gamma were expressed in the myocardium while others, like IL-4 were not. In conclusion, an orchestrated complex of immune mechanisms seems to be the basis of IDC etiopathogenesis. (C) 2001 Academic Press.
引用
收藏
页码:3 / 13
页数:11
相关论文
共 28 条
[1]
BER-MAC3 - NEW MONOCLONAL-ANTIBODY THAT DEFINES HUMAN MONOCYTE MACROPHAGE DIFFERENTIATION ANTIGEN [J].
BACKE, E ;
SCHWARTING, R ;
GERDES, J ;
ERNST, M ;
STEIN, H .
JOURNAL OF CLINICAL PATHOLOGY, 1991, 44 (11) :936-945
[2]
EVIDENCE FOR SUPERANTIGEN INVOLVEMENT IN INSULIN-DEPENDENT DIABETES-MELLITUS ETIOLOGY [J].
CONRAD, B ;
WEIDMANN, E ;
TRUCCO, G ;
RUDERT, WA ;
BEHBOO, R ;
RICORDI, C ;
RODRIQUEZRILO, H ;
FINEGOLD, D ;
TRUCCO, M .
NATURE, 1994, 371 (6495) :351-355
[3]
Sequence-specific priming and exonuclease-released fluorescence detection of HLA-DQB1 alleles [J].
Faas, SJ ;
Menon, R ;
Braun, ER ;
Rudert, WA ;
Trucco, M .
TISSUE ANTIGENS, 1996, 48 (02) :97-112
[4]
DIAGNOSIS AND CLASSIFICATION OF MYOCARDITIS BY ENDOMYOCARDIAL BIOPSY [J].
FENOGLIO, JJ ;
URSELL, PC ;
KELLOGG, CF ;
DRUSIN, RE ;
WEISS, MB .
NEW ENGLAND JOURNAL OF MEDICINE, 1983, 308 (01) :12-18
[5]
NEGATIVE INOTROPIC EFFECTS OF CYTOKINES ON THE HEART MEDIATED BY NITRIC-OXIDE [J].
FINKEL, MS ;
ODDIS, CV ;
JACOB, TD ;
WATKINS, SC ;
HATTLER, BG ;
SIMMONS, RL .
SCIENCE, 1992, 257 (5068) :387-389
[6]
Interleukin-1 in myocardium and coronary arteries of patients with dilated cardiomyopathy [J].
Francis, SE ;
Holden, H ;
Holt, CM ;
Duff, GW .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1998, 30 (02) :215-223
[7]
HENKE A, 1992, J IMMUNOL, V148, P2270
[8]
DETECTION OF ENTEROVIRUS RNA IN MYOCARDIAL BIOPSIES FROM PATIENTS WITH MYOCARDITIS AND CARDIOMYOPATHY USING GENE AMPLIFICATION BY POLYMERASE CHAIN-REACTION [J].
JIN, O ;
SOLE, MJ ;
BUTANY, JW ;
CHIA, WK ;
MCLAUGHLIN, PR ;
LIU, P ;
LIEW, CC .
CIRCULATION, 1990, 82 (01) :8-16
[9]
KAMMERER U, 1994, J CLIN MICROBIOL, V32, P285
[10]
Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy [J].
Kuhl, U ;
Noutsias, M ;
Seeberg, B ;
Schultheiss, HP .
HEART, 1996, 75 (03) :295-300