Abstract
To evaluate the cellular composition of Quilty lesions in heart transplant biopsies and their association with acceptance or rejection of cardiac allografts. In this study we included a cohort of cardiac transplant biopsies with Quilty lesions for which a final diagnosis had already been rendered for treatment purposes. Serial sections from 42 specimens were stained immunohistochemically for CD4, CD8, FoxP3 (as surrogate marker of innate regulatory T cells) and TGF-beta-1 (as surrogate marker of adaptive regulatory immune cells). The relative abundance of cells positive for each of these four markers was evaluated both in the Quilty lesion itself and in the uninvolved, surrounding myocardium using semi-quantitative methods. Correlations were then made, using chi-square and Pearson analysis, between these measures and allograft acceptance. FoxP3+ (OR 1.33, p<0.05) and TGF-beta+ cells (OR 1.4) in the quilty lesions are associated with higher allograft acceptance. Of note, no FoxP3+ cells were seen in myocardium. However, the presence of CD8+ cells in the myocardium is associated with greater degrees of both acute cellular (p<0.02) and antibody-mediated transplant rejection (p<0.04). High numbers of CD4+ cells in the myocardium are also associated with a greater degree of acute cellular rejection (p<0.04). However, the presence of either CD4+ or CD8+ T-cells in Quilty lesions are not associated with rejection. Interestingly, greater numbers of TGF-beta-positive cells in the myocardium are associated with a greater degree of antibody-mediated rejection. Quilty lesions previously have been associated with mild to moderate acute cellular rejection, but their precise function remains unclear: it has yet to be determined whether they might participate in immune-mediated tissue destruction or may represent an immune-mediated tissue salvage mechanism. In this study, both FoxP3+ innate and TGF-beta+ adaptive regulatory cells are associated with increased allograft acceptance in biopsies when localize? in quilty lesions. Myocardial effector CD4+ and CD8+ T-cells are associated with increased rejection. However, their presence in quilty lesions has no effect in rejection or acceptance or the transplant. Therefore, quilty lesions may rather represent intragraft tertiary lymphoid tissue to prevent allograft rejection, and assist in acceptance of the organ transplant. Drs. George and Anne Race Distinguished Professor of Pathology Endowment Fund (Dr. Jose Torrealba).
Published Version
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