Donor-specific Immune Regulation by CD8+ Lymphocytes Expanded from Rejecting Human Cardiac Allografts |
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Authors: | I. E. Dijke K. Caliskan M. Klepper R. de Kuiper A. H. M. M. Balk A. P. W. M. Maat W. Weimar C. C. Baan |
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Affiliation: | Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam,The Netherlands;Department of Cardiology, Erasmus MC, University Medical Center Rotterdam,The Netherlands;Department of Thoracic Surgery, Erasmus MC, University Medical Center Rotterdam,The Netherlands |
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Abstract: | To assess whether regulatory T cells are present in rejecting human cardiac allografts, we performed functional analyses of graft lymphocytes (GLs) expanded from endomyocardial biopsies (EMB; n = 5) with histological signs of acute cellular rejection. The GL cultures were tested for their proliferative capacity and regulatory activity on allogeneic-stimulated peripheral blood mononuclear cells (PBMC) of the patient (ratio PBMC:GLs = 5:1). Three of these GL cultures were hyporesponsive to donor antigens and suppressed the antidonor proliferative T-cell response of PBMC, but not the anti-third-party response. Interestingly, it was the CD8+ GL subset of these cultures that inhibited the antidonor response (65–91% inhibition of the proportion of proliferating cells); the CD4+ GLs of the expanded GL cultures were not suppressive. In conclusion, CD8+ GLs expanded from rejecting human cardiac allografts can exhibit donor-specific immune regulatory activities in vitro . We suggest that during acute cellular rejection, GLs may not only consist of graft-destructing effector T cells, but also of cells of the CD8+ type with the potential to specifically inhibit antidonor immune reactivity. |
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Keywords: | Acute cellular rejection antigen-specificity endomyocardial biopsy graft-infiltrating lymphocytes heart transplantation human immune regulation |
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