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- Title
Cytotoxic perforin+ and TIA-1+ infiltrates are associated with cell adhesion molecule expression in dilated cardiomyopathy
- Authors
Noutsias, Michel; Pauschinger, Matthias; Schultheiss, Heinz-Peter; Kühl, Uwe; Kühl, Uwe
- Abstract
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 naı¨ve CD3 T-lymphocytes.
- Subjects
CELL adhesion; LYMPHOCYTES; CARDIOMYOPATHIES; INFLAMMATION; CELL communication; CELL adhesion molecules; CELL receptors; COMPARATIVE studies; ENDOTHELIUM; IMMUNOHISTOCHEMISTRY; RESEARCH methodology; MEDICAL cooperation; POLYMERASE chain reaction; PROTEINS; RESEARCH; T cells; PHENOTYPES; EVALUATION research; REVERSE transcriptase polymerase chain reaction; MEMBRANE glycoproteins; DILATED cardiomyopathy; CYTOTOXINS
- Publication
European Journal of Heart Failure, 2003, Vol 5, Issue 4, p469
- ISSN
1388-9842
- Publication type
journal article
- DOI
10.1016/S1388-9842(03)00037-0