Mignon-Godefroy K, Brazillet M P, Rott O, Charreire J
INSERM U.283, Hôpital Cochin, Paris, France.
Cell Immunol. 1995 May;162(2):171-7. doi: 10.1006/cimm.1995.1066.
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.
实验性自身免疫性甲状腺炎（EAT）的特征是自身反应性T和B细胞应答、甲状腺显著的淋巴细胞浸润以及出现针对甲状腺球蛋白的循环自身抗体。淋巴细胞参与其中的直接证据源于以下观察结果：通过转移从鼠甲状腺球蛋白（mTg）免疫的供体获得的体外再刺激效应脾细胞，可在未经处理的、经照射的CBA/J小鼠中诱导出EAT。利用这种转移EAT（tEAT）模型，我们研究了在mTg体外再刺激过程中添加重组鼠白细胞介素-4（rIL-4）或人白细胞介素-10（rIL-10）是否会影响随后疾病的诱导。为了确定在与mTg和细胞因子进行二次体外孵育期间诱导的变化，研究了对mTg的增殖和细胞毒性应答。与在无细胞因子条件下培养的mTg激活细胞相比，用mTg和rIL-4培养的mTg激活细胞对mTg的增殖应答仅略有降低，而对mTg脉冲巨噬细胞的细胞毒性应答增加。相比之下，当细胞与mTg和rIL-10一起培养时，对mTg的增殖和细胞毒性应答分别降低了约45%和85%。将在rIL-10存在下培养的mTg激活脾细胞注射到经照射的CBA/J小鼠中，与注射未经细胞因子培养的mTg激活细胞的受照射宿主相比，受体甲状腺的淋巴细胞浸润显著减少（P = 0.02），但体内抗mTg自身抗体的产生没有减少。相比之下，当给小鼠注射用mTg和rIL-4培养的mTg激活细胞时，受体甲状腺的淋巴细胞浸润与对照组相似，但循环抗mTg抗体却惊人地显著减少。这些结果表明，在相同实验条件下，两种典型的“Th2细胞因子”，即IL-4和IL-10，在体外添加到mTg特异性脾细胞时，在细胞毒性mTg特异性T细胞反应性的增强或减弱以及随后tEAT严重程度的维持或减轻方面可产生相当不同的影响。
