© 2003 European Society of Cardiology
Cytotoxic perforin+ and TIA-1+ infiltrates are associated with cell adhesion molecule expression in dilated cardiomyopathy
Department of Cardiology and Pneumonoly, University Hospital Benjamin Franklin Free University of Berlin, Hindenburgdamm 30 Berlin D-12200, Germany
* Corresponding author. Tel.: +49-30-8445-2344; fax: +49-30-8445-3565 E-mail address: noutsias{at}zedat.fu-berlin.de
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Abstract |
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Objective: To phenotypically characterize cytotoxic T-lymphocytes (CTLs: Perforin+ and TIA-1+ phenotypes) and to study the interactions with cell adhesion molecules (CAMs) in dilated cardiomyopathy (DCM).
Background: DCM is linked to intramyocardial inflammation, being characterized by T-lymphocytic infiltration and CAMs abundance. However, the pathogenic significance of increased CD3+ lymphocytes remains obscure as these do not correlate with CTLs (perforin+ and TIA1+ phenotypes). CAMs participate in the phenotypic repertoire and effector pathways of CTLs.
Methods: CAMs-expression (ICAM-1, VCAM-1, LFA-3, CD29, CD62E and CD62P and β2-integrins), CD3+ (T-lymphocytes), CD57+ (NK-cells) and adhesion related (CD18+, CD11a+, CD11b+, CDw49d+) phenotyped infilitrates were investigated in endomyocardial biopsies (EMBs) from 89 DCM patients (33 female; LVEF<40%) using immunohistochemisty. The enteroviral genome was identified by nested RT-PCR.
Results: CAMs abundance was confirmed in 55 DCM patients (62%) and 29 EMBs (33%) were graded CTLs+ (>1.5 TIA-1+ and/or >2.0 perforin+ infiltrates/hpf). CTLs correlated with all endothelial CAMs-markers studied (P<0.01), the adhesion related phenotypes of infilitrates (LFA-1, VLA-4, CD18) and CD57+ NK-cells (P<0.02). There was no correlation of CTLs with CD3+ T-lymphocytes, CD11b+ macrophages, enteroviral infection (present in n=16/18%), clinical history and LVEF (P>0.05). Phenomena suggestive of CTLs mediated myocytolysis were observed in 10 patients (11%).
Conclusions: CTLs-infilitrates are associated with endothelial CAMs-abundance and co-express adhesion related (β2-integrins, VLA-4) and NK-cellular antigens (CD57) in DCM. Endothelial CAMs expression also reflects cytotoxic activation of intramyocardial infilitrates, which is not reflected by immunologically naïve CD3 T-lymphocytes.
Key Words: Abbreviations • DCM, dilated cardiomyopathy • InfCM, inflammatory cardiomyopathy • CAMs, cell adhesion molecules • CTLs, cytotoxic T-lymphocytes • ICAM-1, intercellular cell adhesion molecule-1 • LFA, lymphocyte function antigen • VCAM-1, vascular cell adhesion molecule-1 • VLA-4, very late activation antigen-4 • HPF, high power field (0.28 mm2) • RT-PCR, reverse transcriptase polymerase chain reaction
Received September 10, 2002; Revised October 24, 2002; Accepted January 23, 2003
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