Enhanced lymphocyte longevity and absence of proliferation and lymphocyte apoptosis in Quilty effects of human heart allografts.
"Quilty effect" (QE) is a common and problematic observation in endomyocardial biopsy specimens from patients after cardiac transplantation. The origin, fate, and significance of QE cellular elements are unknown. Twenty-six paraffin-embedded endomyocardial biopsy specimens with QE (five QE As and twenty-one QE Bs) from twenty-two cardiac allografts were studied by immunohistochemistry for expression of Bcl-2, Fas antigen, proliferating cell nuclear antigen (PCNA), perforin, T cells (UCHL-1), macrophages (CD68), and apoptosis by in situ terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL). Approximately 50% of the lymphocytes present, mainly in the deeper region of 20 of 21 QE Bs and all 5 QE As, expressed Bcl-2 in a pseudo-nodular pattern surrounding high endothelial venules. Fas expression was detected in lymphocytes in 20 of 21 QE Bs and 5 QE As in a similar pattern to Bcl-2. However, endothelial cells and macrophages were Bcl-2 negative, whereas both cell types were Fas positive. Perforin was negative in nearly all lymphocytes. TUNEL staining revealed that lymphocytes in QEs did not undergo apoptosis; however, TUNEL positivity was observed in approximately 70% of endothelial cells and macrophages and certain adjacent cardiac myocytes in 20 of 21 QE Bs and 5 QE As. One large QE B with a germinal center was noted. Germinal center cells expressed PCNA intensely but were negative for Bcl-2, Fas, and TUNEL. Cells surrounding the germinal center expressed abundant Bcl-2. The following conclusions were drawn. 1) Apoptosis does not occur in lymphocytes in QE where enhanced Bcl-2 (apoptosis inhibitor) and Fas antigen (apoptosis inducer) are expressed. 2) PCNA negativity indicates that QE lymphocytes may not proliferate, and perforin negativity indicates that they may not exhibit perforin-based cytotoxicity. We propose that there may be a relationship between the longevity of lymphocytes in QE and the absence of apoptosis.
Dong
C
C
Department of Pathology and Laboratory Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Winters
G L
GL
Wilson
J E
JE
McManus
B M
BM
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D004699:Endocardium / Q000276:immunology / Q000473:pathology*; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000096:biosynthesis
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D054353:Perforin; D017493:Leukocyte Common Antigens