Cytotoxic perforin+ and TIA-1+ infiltrates are associated with cell adhesion molecule expression in dilated cardiomyopathy.
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 beta(2)-integrins), CD3+ (T-lymphocytes), CD57+ (NK-cells) and adhesion related (CD18+, CD11a+, CD11b+, CDw49d+) phenotyped infiltrates 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 infiltrates (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-infiltrates are associated with endothelial CAMs-abundance and co-express adhesion related (beta2-integrins, VLA-4) and NK-cellular antigens (CD57) in DCM. Endothelial CAMs expression also reflects cytotoxic activation of intramyocardial infiltrates, which is not reflected by immunologically nai;ve CD3 T-lymphocytes.
Noutsias
Michel
M
Department of Cardiology and Pneumonoly, University Hospital Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30 D-12200, Berlin, Germany. noutsias@zedat.fu-berlin.de
Pauschinger
Matthias
M
Schultheiss
Heinz-Peter
HP
Kühl
Uwe
U
D000368:Aged; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D018959:CD57 Antigens / Q000276:immunology / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D018821:CD18 Antigens; D017252:CD3 Complex; D018959:CD57 Antigens; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin