Distinctive modulation by IL-4 and IL-10 of the effector function of murine thyroglobulin-primed cells in "transfer-experimental autoimmune thyroiditis".

Experimental autoimmune thyroiditis (EAT) is characterized by autoreactive T and B cell responses, a marked lymphocytic infiltration of the thyroid gland, and the occurrence of circulating autoantibodies to thyroglobulin. Direct evidence for the involvement of lymphocytes stems from the observation that EAT can be induced in naive, irradiated CBA/J mice by transfer of in vitro restimulated effector spleen cells obtained from murine thyroglobulin (mTg)-immunized donors. Using this transfer-EAT (tEAT) model, we have investigated whether addition of recombinant murine IL-4 (rIL-4) or human IL-10 (rIL-10) during the in vitro restimulation by mTg would affect the subsequent induction of the disease. To determine the modification(s) induced during the secondary in vitro incubation with mTg and cytokine, proliferative and cytotoxic responses to mTg were studied. MTg-activated cells cultured with mTg and rIL-4 exhibited only slightly decreased proliferative responses to mTg and increased cytotoxic responses toward mTg-pulsed macrophages compared to mTg-activated cells cultured in the absence of cytokine. In contrast, proliferative and cytotoxic responses to mTg were diminished by approximately 45 and 85%, respectively, when cells were cultured with mTg and rIL-10. The injection of mTg-activated spleen cells, cultured in the presence of rIL-10, into irradiated CBA/J mice induced a significant decrease (P = 0.02) in lymphocytic infiltrations of the recipient thyroid glands compared to injection of irradiated hosts with mTg-activated cells cultured without cytokines, but no reduction in anti-mTg autoantibody production in vivo. In contrast, when mice were injected with mTg-activated cells cultured with mTg and rIL-4, the lymphocytic infiltrations of the recipient thyroid glands were similar to controls, but circulating anti-mTg antibody were surprisingly significantly reduced. These results show that two typical "Th2 cytokines," IL-4 and IL-10, when added in vitro to mTg-specific spleen cells under identical experimental conditions, can have rather diverse effects in terms of an exacerbation or weakening of cytotoxic mTg-specific T cell reactivity and a maintenance or attenuation of subsequent tEAT severity.