The effect of methimazole, iodine and splenocytes on thyroid transplants in BB/Wor rats

Background. BB/Wor rats develop spontaneous autoimmune insulin-requiring di abetes mellitus and lymphocytic thyroiditis (LT). Our investigations examin ed the effect of the thyroid-specific agents, iodine and methimazole (MMI) on thyroid graft survival in BB/Wor rats, compared the intrathyroidal cytok ine mRNA expression of endogenous and engrafted thyroids, and ascertained w hether unfractionated splenocytes could protect thyroid grafts from lymphoc ytic infiltration. Methods. In study 1, 0.025% iodine water-treated LT-prone NE Line BB/Wor ra ts were randomized to receive one of the following treatments: (1) 1.0 x 10 (8) splenocytes, TV from LT-resistant WA line BB/Wor rats, (2) WA rat thyro id transplants, (3) both, or (4) neither (controls), In study 2, after thyr oid transplantation, LT-prone BB/Wor rats were randomized to receive (1) WA splenocytes, (2) 0.025% iodine water, (3) 0.05% MMI water or, (4) tap wate r (controls). The incidence of LT was determined by microscopic inspection after hematoxylin and eosin staining. Lymphocytic infiltrates were characte rized by immunohistochemistry. Cytokine mRNA was detected by RT-PCR. Results. Grafts from MMI-treated rats had a significantly lower incidence o f lymphocytic infiltration (MMI: 2/5; Tap: 5/5; I 5/5, P < 0.05, chi(2)). I L-10 mRNA was expressed in 77% (7/9) endogenous thyroids and 20% (1/5) of t he transplanted WA thyroids (P < 0.05, chi(2)) from iodine-treated rats wit h LT, There was no difference in IL-12 mRNA expression, Lymphocytic infiltr ation occurred in 100% of the splenocyte;treated graft recipients. Both end ogenous and engrafted thyroids contained CD4 and C8 T cells with scattered IgG staining. Conclusion. Target organ-specific interventions that suppress antigen prese ntation may have an adjunctive role in transplantation tolerance. The diffe rential expression of IL-10 may indicate preferential Th2 lymphocyte activa tion in the endogenous tissues.