Pretreatment of transfused donor splenocytes and allografts with mitomycin c attenuates acute rejection in heart transplantation in mice

L. Liu, F. Wang, Y. Zheng, X. Yuan, D. Wang, W. Zeng, X. He, C. Wang, S. Deng

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Objective The aim of this study was to investigate the effect of pretreatment of donor splenocytes and grafts with mitomycin C (MMC) on heart allograft survival, as well as to demonstrate the mechanism of function. Methods Donor splenocytes from Balb/C mice were incubated with MMC (40 μg/mL) in vitro and then transfused into recipients (C57BL/6 mice). The heart allograft was perfused with MMC before harvest. Graft survival and histopathology were examined. Lymphocyte activation, regulatory T cells, and donor splenocyte apoptosis were examined with the use of flow cytometry. Results MMC incubation in vitro induced apoptosis of donor splenocytes (15.5 ± 2.3% vs 23.2 ± 4.2%; P <.01). Either intravenous injection of MMC-treated donor splenocytes or transplantation of allograft pretreated with MMC prolonged heart allograft mean survival time from 7 ± 0.8 days to 20.5 ± 1.9 days or 10 ± 0.9 days, respectively (both P <.01). A combination of MMC-pretreated donor splenocyte transfusion and allografts showed the best effect on prolongation of graft survival (28.5 ± 1.8 days). Activation of CD4+ T cells in spleen and peripheral lymph nodes of recipients was significantly inhibited by either MMC-splenocyte transfusion or the combination treatment. Meanwhile, the percentage of CD4+CD25 +Foxp3+ regulatory T cells in the spleen was increased in the MMC-splenocyte transfusion group (15.5 ± 1.1% vs 18.2 ± 0.9%; P <.05). Conclusions Both injection of MMC-conditioned donor splenocytes and MMC-conditioned allograft have effects on prolongation of heart allograft survival in mice, and MMC-conditioned donor splenocytes might play an essential role. MMC pretreatment induced regulatory T cells likely through induction of donor splenocyte apoptosis, and thus it inhibited T-cell activation.

Original languageEnglish (US)
Pages (from-to)1169-1174
Number of pages6
JournalTransplantation Proceedings
Volume46
Issue number4
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Fingerprint Dive into the research topics of 'Pretreatment of transfused donor splenocytes and allografts with mitomycin c attenuates acute rejection in heart transplantation in mice'. Together they form a unique fingerprint.

Cite this