IL-10 Kinetics in Thyroiditis-Prone BB/Wor Rats

Abstract

Cytokines modulate the course of autoimmunity, but their role in the evolution of spontaneous disease is unclear. This study compared the cytokine kinetics of T cell cultures from thyroiditis (LT)-prone NB line BB/Wor rats with those of Wistar (Wis) rat controls following activation with the thyroid-specific antigen thyroglobulin (Tg) or Concanavalin A (Con A). Design: T cell enhanced splenocytes from 60 day old Wis and NB rats were activated with 0.5 μg/ml rat thyroglobulin (Tg) or Con A in the presence of homologous irradiated splenocytes as antigen presenting cells (APC's). In addition, the effect of APC's was determined in a crisscross experiment which examined NB T cell responses to Con A in the presence of Wis APC's. ELISA and RT-PCR were used to examine IL-2, IL-4, IL-10, TNFα, IFNγ, IL-10 concentrations and mRNA expression in the supernatant and cells from parallel cultures harvested at specific intervals. Frozen thyroids from 60 day old NB, Wis and Fisher rats were examined for the presence of IL-10 by immunohistochemistry. T cell proliferation was measured by H thymidine uptake. Results: Following activation with either Tg or Con A, IL-10 concentrations exceeded IFNγ in NB rat cultures, but IFNγ exceeded IL-10 in Wis cultures. Wis splenocytes significantly enhanced NB T cell proliferation and cytokine responses to Con A. Thyroids from 60 day NB rats contained IL-10, but no IFNγ. There was no IL-10 in thyroids from Wistar or Fisher rats. Conclusion: Splenocyte responses in LT-prone BB/Wor rats favor IL-10 production. Future investigations will examine the source of intrathyroidal IL-10 and its role in LT