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

Background: BB/Wor rats develop spontaneous autoimmune insulin-requiring diabetes mellitus and lymphocytic thyroiditis (LT). Our investigations examined the effect of the thyroid-specific agents, iodine and methimazole (MMI) on thyroid graft survival in BB/Wor rats, compared the intrathyroidal cytokine mRNA expression of endogenous and engrafted thyroids, and ascertained whether unfractionated splenocytes could protect thyroid grafts from lymphocytic infiltration.

Methods: In study 1, 0.025% iodine water-treated LT-prone NB line BB/Wor rats were randomized to receive one of the following treatments: (1) 1.0 x 10(8) splenocytes, IV from LT-resistant WA line BB/Wor rats, (2) WA rat thyroid transplants, (3) both, or (4) neither (controls). In study 2, after thyroid 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 water (controls). The incidence of LT was determined by microscopic inspection after hematoxylin and eosin staining. Lymphocytic infiltrates were characterized by immunohistochemistry. Cytokine mRNA was detected by RT-PCR.

Results: Grafts from MMI-treated rats had a significantly lower incidence of lymphocytic infiltration (MMI: 2/5; Tap: 5/5; I 5/5, P<0.05, chi2). IL-10 mRNA was expressed in 77% (7/9) endogenous thyroids and 20% (1/5) of the transplanted WA thyroids (P<0.05, chi2) from iodine-treated rats with LT. There was no difference in IL-12 mRNA expression. Lymphocytic infiltration occurred in 100% of the splenocyte-treated graft recipients. Both endogenous and engrafted thyroids contained CD4 and C8 T cells with scattered IgG staining.

Conclusion: Target organ-specific interventions that suppress antigen presentation may have an adjunctive role in transplantation tolerance. The differential expression of IL-10 may indicate preferential Th2 lymphocyte activation in the endogenous tissues.