ANALYSIS OF CYTOKINE MESSENGER-RNA EXPRESSION IN SYNGENEIC ISLET GRAFTS OF NOD MICE - INTERLEUKIN-2 AND INTERFERON-GAMMA MESSENGER-RNA EXPRESSION CORRELATE WITH GRAFT-REJECTION AND INTERLEUKIN-10 WITH GRAFT-SURVIVAL

The injection of complete Freund's adjuvant into diabetic nonobese dia betic (NOD) mice at the time of syngeneic islet transplantation preven ts monocytic/lymphocytic cell infiltration into the islet graft, Beta- cell destruction, and autoimmune diabetes recurrence. We have used sem iquantitative reverse transcriptase-polymerase chain reaction analysis to examine and compare cytokine mRNA expression profiles in islet gra fts from complete Freund's adjuvant-injected and control NOD mice. Int erleukin 10 mRNA expression was significantly increased whereas interl eukin 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 mic e. These findings suggest that a Th1 subset of lymphocytes and their c ytokine 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 conseq uent down-regulation of Th1 cells and cytokines in the islet graft.