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Analysis of cytokine mRNA expression in syngeneic islet grafts of NOD mice: interleukin 2 and interferon gamma mRNA expression correlate with graft rejection and interleukin 10 with graft survival

Summary

The injection of complete Freund's adjuvant into diabetic nonobese diabetic (NOD) mice at the time of syngeneic islet transplantation prevents monocytic/lymphocytic cell infiltration into the islet graft, Beta-cell destruction, and autoimmune diabetes recurrence. We have used semiquantitative reverse transcriptase-polymerase chain reaction analysis to examine and compare cytokine mRNA expression profiles in islet grafts from complete Freund's adjuvant-injected and control NOD mice. Interleukin 10 mRNA expression was significantly increased whereas interleukin 2 and interferon gamma mRNA levels were significantly decreased in islet grafts from complete Freund's adjuvant-injected mice compared to control mice. Levels of mRNA for interleukin 1 beta, interleukin 4, and tumour necrosis factor alpha were not significantly different in islet grafts from complete Freund's adjuvant-injected and control mice. These findings suggest that a Th1 subset of lymphocytes and their cytokine products, interleukin 2 and interferon gamma, may be involved in the rejection of syngeneic islet grafts and diabetes recurrence in NOD mice, and that the protective effect of complete Freund's adjuvant may result from the induction of interleukin 10 production and consequent down-regulation of Th1 cells and cytokines in the islet graft.

Abbreviations

NOD:

Nonobese diabetic mouse

CFA:

complete Freund's adjuvant

PCR:

polymerase chain reaction

IL:

interleukin

TNFα:

tumour necrosis factor alpha

IFNγ :

interferon gamma

BBrat:

bio-breeding rat

PBS:

phosphate buffered saline

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Rabinovitch, A., Sorensen, O., Suarez-Pinzon, W.L. et al. Analysis of cytokine mRNA expression in syngeneic islet grafts of NOD mice: interleukin 2 and interferon gamma mRNA expression correlate with graft rejection and interleukin 10 with graft survival. Diabetologia 37, 833–837 (1994). https://doi.org/10.1007/BF00404341

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  • DOI: https://doi.org/10.1007/BF00404341

Key words

  • Nonobese diabetic mouse
  • islet transplantation
  • cytokines