THE QUILTY-LESION ENIGMA - FOCAL APOPTOSIS NECROSIS AND LYMPHOCYTE SUBSETS IN HUMAN CARDIAC ALLOGRAFTS/

Quilty lesions, as first described by Billingham in 1981, or 'Quilty E ffect' (QE) are distinct endomyocardial mononuclear cell infiltrates t hat have been observed in human heart transplant recipients, as well a s in experimental models of heart transplantation. In the present inve stigations, the pattern and extent of apoptosis (programmed cell death ) and myocyte necrosis, as well as specific lymphocyte subsets in Quil ty lesions was assessed, Endomyocardial biopsies obtained from 13 pati ents at 10-3362 days post-transplant were examined, Apoptosis, as iden tified by DNA nick end-labeling, was found in myocytes at the peripher y of Quilty lesions in 11 of 13 cases (85%), and 'early' stages of myo cyte necrosis, as demonstrated by specific staining with alpha light c hain myosin monoclonal antibodies (mAb), was observed at the same site s in 10 of 13 cases (77%) of both Quilty type A and type B lesions. Ap optosis was not identified in the lymphocyte infiltrates of any of the lesions examined. Lymphocyte subsets were characterized using mAb for T cell receptor (CD3), for helper/inducer T cells (CD4), for cytotoxi c/supressor T cells (CD8) and for mature B cells (CD20). Immunostainin g revealed separate clusters of T lymphocytes with less prevalent B ce lls within the Quilty lesions. CD4(+) cells were found in larger numbe rs than CD8(+) cells in all cases. Non-B, non-T large lymphocytes were occasionally present. Except for the extent of the cellular infiltrat e, no major cytochemical lymphocyte distribution differences were foun d between Quilty type A and B lesions, Myocyte apoptosis and early nec rosis at the periphery of Quilty lesions suggest that early myocyte in jury occuring in B lesions may represent initial or 'abortive stages' of cardiac allograft rejection, Why these lesions do not progress to o vert rejection indeed warrant further detailed studies.