The Quilty lesion enigma: Focal apoptosis/necrosis and lymphocyte subsets in human cardiac allografts

Abstract

Quilty lesions, as first described by Billingham in 1981, or 'Quilty Effect' (QE) are distinct endomyocardial mononuclear cell infiltrates that have been observed in human heart transplant recipients, as well as in experimental models of heart transplantation. In the present investigations, the pattern and extent of apoptosis (programmed cell death) and myocyte necrosis, as well as specific lymphocyte subsets in Quilty lesions was assessed. Endomyocardial biopsies obtained from 13 patients at 10-3362 days post-transplant were examined. Apoptosis, as identified by DNA nick end-labeling, was found in myocytes at the periphery of Quilty lesions in 11 of 13 cases (85%), and 'early' stages of myocyte necrosis, as demonstrated by specific staining with alpha light chain myosin monoclonal antibodies (mAb), was observed at the same sites in 10 of 13 cases (77%) of both Quilty type A and type B lesions. Apoptosis 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 cytotoxic/suppressor T cells (CD8) and for mature B cells (CD20). Immunostaining revealed separate clusters of T lymphocytes with less prevalent B cells within the Quilty lesions. CD4+ cells were found in larger numbers than CD8+ cells in all cases. Non-B, non-T large lymphocytes were occasionally present. Except for the extent of the cellular infiltrate, no major cytochemical lymphocyte distribution differences were found between Quilty type A and B lesions. Myocyte apoptosis and early necrosis at the periphery of Quilty lesions suggest that early myocyte injury occurring in B lesions may represent initial or 'abortive stages' of cardiac allograft rejection. Why these lesions do not progress to overt rejection indeed warrant further detailed studies.

Quilty Indicates Increased Risk for Microvasculopathy and Poor Survival After Heart Transplantation

“…This finding may have been due to an agingrelated decrease of B-cells, 26 which represent one major cell line in Quilty lesions. 10,29 As reported elsewhere, 2,3 Quilty was found to be associated with acute cellular rejection, and was suggested to represent sub-clinical rejection. 30 Women have been shown to be more likely to develop acute cellular rejections, 31 and we found them more likely to be Quilty-positive than men, which might be related to a higher "baseline immunoreactivity" in females.…”

Quilty Effect Correlates With Biopsy-proven Acute Cellular Rejection But Does Not Predict Transplanted Heart Coronary Artery Vasculopathy

“…11 The attempts to use an ancillary DNA nicking procedure for differentiation between QE and rejection infiltrates produced ambiguous results. Gopal et al, 12 using DNA nick-end labeling, showed increased apoptotic activity at the periphery of Quilty lesions in 85% of their cases, whereas Dong et al 13 demonstrated an absence of apoptosis and increased longevity of QE lymphocytes. Thus, we did not perform additional differential immunostaining with transferase dUTP-mediated nick-end labeling (TUNEL) or in situ end labeling (ISEL) techniques.…”

Simultaneous LFA-1 and CD40 Ligand Antagonism Prevents Airway Remodeling in Orthotopic Airway Transplantation: Implications for the Role of Respiratory Epithelium as a Modulator of Fibrosis

“…T lymphocytes have been well demonstrated to be precursory to tissue damage, and yet it is quite common to note an accumulation of lymphocytes without subsequent tissue damage. An example of lymphocyte accumulations not known to progress to transplant damage is the Quilty lesion in heart transplantation (48). Colonizing T cells in transplants have been shown to contain members with regulatory function that can prevent nontolerant lymphocytes from rejecting transplanted allografts (49).…”