2006-08-01
Donor-specific Cytotoxic Hyporesponsiveness Associated With High Interleukin-10 Messenger RNA Expression in Cardiac Allograft Patients
Publication
Publication
The Journal of Heart and Lung Transplantation , Volume 25 - Issue 8 p. 955- 964
Background: After transplantation, CD4+CD25+FOXP3+ and interleukin (IL) 10-producing regulatory cells might regulate immune responses toward donor antigens. In this study, we determined whether cardiac allograft recipients show donor-specific hyporesponsiveness and studied the underlying mechanisms. Methods: We analyzed the donor-specific T-cell responses by mixed lymphocyte reactions and limiting dilution assays to define whether cardiac allograft recipients (n = 21) show proliferative and cytotoxic hyporesponsiveness to donor antigens long after transplantation (range, 1.5-7 years). The mechanisms controlling immune responses, that is, FOXP3+/GITR+ T cells, and IL-10-producing cells, were studied by quantitative real-time polymerase chain reaction. Results: In the presence of a proliferative response to donor antigens, no cytotoxic responsiveness could be measured in a number of patients in the absence (73%) and presence of exogenous IL-2 (29%), IL-15 (31%), and IL-15 plus IL2Rα blockade (88%). Overall, the cytotoxic response to donor cells was significantly lower than the reactivity to third-party cells after the addition of IL-2 (p = 0.004) and IL-15 plus IL2Rα blockade (p < 0.001). After donor stimulation, the peripheral blood mononuclear cells expressed higher messenger RNA (mRNA) levels of IL-10, but not of FOXP3 or GITR, than after third-party stimulation (p = 0.003). Moreover, the IL-10 mRNA expression was inversely correlated with the donor-specific cytotoxic responsiveness (p = 0.01). Conclusions: A significant proportion of patients showed donor-specific cytotoxic hyporesponsiveness long after heart transplantation, which was associated with high mRNA levels of IL-10 but not of FOXP3 or GITR. This observation suggests that IL-10-producing cells participate in the donor-specific cytotoxic hyporeactivity.
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| doi.org/10.1016/j.healun.2006.03.021, hdl.handle.net/1765/55072 | |
| The Journal of Heart and Lung Transplantation | |
| Organisation | Department of Cardio-Thoracic Surgery |
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Dijke, E., Veldhuis, J., Balk, A., Korevaar, S., Maat, A., Weimar, W., & Baan, C. (2006). Donor-specific Cytotoxic Hyporesponsiveness Associated With High Interleukin-10 Messenger RNA Expression in Cardiac Allograft Patients. The Journal of Heart and Lung Transplantation, 25(8), 955–964. doi:10.1016/j.healun.2006.03.021 |
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