Weetman A P, Rees A J
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Immunology. 1988 Feb;63(2):285-9.
In this study, we have investigated the effects of tumour necrosis factor (TNF), interferon-gamma (IFN-gamma) and interleukin-1 (IL-1) on rat thyroid cells, using the continuously growing, differentiated FRTL5 cell line. No effect on cell growth was found with any cytokine alone, but the combination of TNF and IFN-gamma was cytostatic. These cells were not killed in a 18-hr assay for cytotoxicity, but prolonged incubation (4 days) with TNF and IFN-gamma produced cell detachment and death. Normal rat thyroid cells in primary culture were also susceptible to the combination of TNF and IFN-gamma for 4 days, but not 18 hr. In addition, IFN-gamma treatment induced class II (Ia) antigens on thyroid cells, and this was enhanced by TNF. TNF alone did not cause Ia expression on thyroid cells but did increase the constitutive expression of class I antigens. These results suggest that IFN-gamma and TNF, which are likely to be released by the lymphocytes and macrophages infiltrating the gland in thyroid autoimmunity, may synergize to impair cell growth and produce aberrant Ia antigen expression in thyroiditis. This could be an important mechanism for disease perpetuation.
在本研究中，我们使用持续生长、分化的FRTL5细胞系，研究了肿瘤坏死因子（TNF）、γ干扰素（IFN-γ）和白细胞介素-1（IL-1）对大鼠甲状腺细胞的影响。单独使用任何一种细胞因子均未发现对细胞生长有影响，但TNF与IFN-γ的组合具有细胞抑制作用。在18小时的细胞毒性试验中，这些细胞未被杀死，但用TNF和IFN-γ长时间孵育（4天）会导致细胞脱离和死亡。原代培养的正常大鼠甲状腺细胞对TNF和IFN-γ的组合作用4天也敏感，但对18小时的作用不敏感。此外，IFN-γ处理可诱导甲状腺细胞上的II类（Ia）抗原表达，而TNF可增强这种作用。单独的TNF不会导致甲状腺细胞上Ia抗原的表达，但会增加I类抗原的组成性表达。这些结果表明，在甲状腺自身免疫中浸润腺体的淋巴细胞和巨噬细胞可能释放的IFN-γ和TNF可能协同作用，损害细胞生长并在甲状腺炎中产生异常的Ia抗原表达。这可能是疾病持续存在的一个重要机制。
