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Cytotoxic perforin+ and TIA‐1+ infiltrates are associated with cell adhesion molecule expression in dilated cardiomyopathy
Author(s) -
Noutsias Michel,
Pauschinger Matthias,
Schultheiss HeinzPeter,
Kühl Uwe
Publication year - 2003
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/s1388-9842(03)00037-0
Subject(s) - perforin , cytotoxic t cell , cell adhesion molecule , medicine , immunology , cd3 , cd18 , dilated cardiomyopathy , cd8 , pathology , integrin alpha m , biology , antigen , immune system , heart failure , in vitro , biochemistry
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 β 2 ‐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.