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Fragile maintenance of allograft tolerance induced by lymphocyte sequestration and co-stimulation blockade

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Authors
Jin, Jizhe; Yang, Seung Hee; Park, Junghwan; Lee, Chungsik; Kim, Sun Moon; Kim, Yon Su; Lee, Jungpyo
Issue Date
2009-09
Publisher
ELSEVIER SCIENCE BV
Citation
TRANSPLANT IMMUNOLOGY; Vol.21 4; 221-227
Keywords
ImmunoregulationLymphocyte sequestrationCo-stimulation blockadeLong-term graft survival
Abstract
The induction of long-term graft survival has been a goal for the last decade. Nevertheless, the issues of stable maintenance of allograft have not yet been evaluated thoroughly. Here, we studied new approaches for induction of tolerance by lymphocyte sequestration (FrY720) and co-stimulatory blockade (MRI) in skin graft model (DBA/2 to BALB/c), thus evaluating the mechanisms incorporated into the maintenance of allograft in proper function. IFTY720 + MR1 treatment significantly prolonged graft survival than single agent treatment did, and induced long-term graft survival in 60% of recipients expressing the up-regulation of IL-4 and FoxP3. To assess the stability of graft maintenance, we performed the second transplantation on recipients that had shown long-term graft survival. While recipients accepted the second graft from the same strain of first donor, the recipients not only rejected the third-party skin (C57BL/6) promptly but also rejected the first graft soon after the third-party skin was transplanted. The expression patterns of IL-4 and FoxP3 were changed according to the strains of second graft in lymph nodes and in the first graft. T(reg) cells from tolerant recipients effectively suppressed allo-antigen driven T cell proliferation, but T(reg) cells from recipients primed with third-party antigen had significantly hampered suppressive capacity against previously tolerant antigens. Our data indicate that the combination treatment provides effective tool for the induction of long-term graft survival, and the maintenance of allograft in proper function is an actively regulated process. (C) 2009 Elsevier B.V. All rights reserved.
ISSN
0966-3274
Language
English
URI
http://hdl.handle.net/10371/76390
DOI
https://doi.org/10.1016/j.trim.2009.06.001
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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