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 endo myocardial biopsy specimens from patients after cardiac transplantatio n. The origin, fate, and significance of QE cellular elements are unkn own. Twenty-six paraffin-embedded endomyocardial biopsy specimens with QE (five QE As and twenty-one QE Bs) from twenty-two cardiac allograf ts were studied by immunohistochemistry for expression of Bcl-2, Fas a ntigen, proliferating cell nuclear antigen (PCNA), perforin, T cells ( UCHL-1), macrophages (CD68), and apoptosis by in situ terminal deoxyri bonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) . Approximately 50% of the lymphocytes present, mainly in the deeper r egion of 20 of 21 QE Bs and all 5 QE As, expressed Bcl-2 in a pseudo-n odular pattern surrounding high endothelial venules. Fas expression wa s detected in lymphocytes in 20 of 21 QE Bs and 5 QE As in a similar p attern to Bcl-2. However, endothelial cells and macrophages were Bcl-2 negative, whereas both cell types were Fas positive. Perforin was neg ative in nearly all lymphocytes. TUNEL staining revealed that lymphocy tes in QEs did not undergo apoptosis; however, TUNEL positivity was ob served in approximately 70% of endothelial cells and macrophages and c ertain adjacent cardiac myocytes in 20 of 21 QE Bs and 5 QE As. One la rge QE B with a germinal center was noted. Germinal center a germinal center was noted. Germinal center cells expressed PCNA intensely but w ere 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 expres sed. 2) PCNA negativity indicates that QE lymphocytes may not prolifer ate, and perforin negativity indicates that they may not exhibit perfo rin-based cytotoxicity. We propose that there may be a relationship be tween the longevity of lymphocytes in QE and the absence of apoptosis.