Islet allograft rejection in sensitized mice is refractory to control by combination therapy of immune-modulating agents
- Authors
- Hong, Juho; Yeom, Hye Jung; Lee, Eunwon; Han, Kyu Hyun; Koo, Tai Yeon; Cho, Bumrae; Ro, Han; Oh, Kook Hwan; Ahn, Curie; Yang, Jaeseok
- Issue Date
- Mar-2013
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- 5-Azacytidine; IL-2/anti-IL-2 complex; Islet transplantation; Memory; Sensitization
- Citation
- TRANSPLANT IMMUNOLOGY, v.28, no.2-3, pp.86 - 92
- Journal Title
- TRANSPLANT IMMUNOLOGY
- Volume
- 28
- Number
- 2-3
- Start Page
- 86
- End Page
- 92
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/14696
- DOI
- 10.1016/j.trim.2013.01.005
- ISSN
- 0966-3274
- Abstract
- Retransplantation is common in allogeneic islet transplantation, and therefore, memory responses in previously sensitized recipients present a distinct obstacle for successful islet transplantation. Given the difficulties in controlling memory responses contributing to allograft rejection, it is worth investigating the effects of new immune-modulating agents against islet allograft rejection in the sensitized recipients. In this study, we investigated immune-modulating agents including 5-azacytidine and IL-2/anti-IL-2 complex to ascertain their suppressive effects on memory responses. In suppression assays, rapamycin effectively suppressed the proliferation of memory T cells, whereas 5-azacytidine, a methylation inhibitor suppressed the survival and proliferation of memory T cells. Combination therapy of anti-CD40L, anti-OX40L, and rapamycin slightly prolonged BALB/c islet allograft survival in sensitized C57BL6 mice, and reduced intragraft infiltration of macrophages, T cells, and B cells. However, the addition of IL-2/anti-IL-2 complex, an inducer of regulatory T cells, did not exhibit additional suppression against rejection in sensitized mice. Although a combination of 5-azacytidine and rapamycin markedly suppressed islet allograft rejection in naive mice, it failed to achieve long-term graft survival even when combined with anti-CD40L and anti-OX40 in sensitized mice. In short, 5-azacytidine-based or IL-2/anti-IL-2 complex-based regimens can suppress islet allograft rejection in naive recipients, but fail to control islet allograft rejection in sensitized recipients. (C) 2013 Elsevier B.V. All rights reserved.
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