Andrada J A, Comini E, Premachandra B N
Clin Exp Immunol. 1973 Feb;13(2):303-26.
The role of the spleen in humoral antibody formation and in the pathogenesis of immune thyroiditis was studied by splenectomizing four monkeys () prior to thyroid isoimmunization. Splenectomized animals, as well as intact controls, were subjected to sequential immunizations and the course of the immune disease was followed by periodic thyroid biopsies and frequent humoral antibody measurements over a period exceeding 1 yr. Extirpation of the secondary lymphoid organ markedly inhibited agglutinating antibody response, prevented formation of complement-fixing antibodies, but had no effect on thyrocytotoxic antibodies. In animals subjected to immunization in complete adjuvant a trend towards a decrease in serum complement levels was evident at the terminal stages of the experiments. Despite the inhibitory effects on some immunological parameters, splenectomy in monkeys prior to thyroid isoimmunization did not interfere with the initiation and progression of pathological processes in the thyroid. Indeed in all splenectomized animals immunized with thyroid plus complete adjuvant, fibrotic thyroid lesions (4+) with virtual obliteration of thyroid follicles were evident, in some as early as 120 days after primary immunization; in contrast, non-fibrotic and less severe lesions were noted in the intact animal despite being repeatedly subjected to similar immunization procedures over a period of 340 days. Immunization in the absence of complete adjuvant did not induce thyroid lesions in the presence or absence of spleen. In all animals with severe thyroid lesions, thyroid function decreased as revealed by T and I-T resin uptake measurements. Paper electrophoresis of serum specimens from a monkey subjected to thyroid isoimmunization in complete adjuvant (and after equilibration with I-T) showed a pronounced retention of I-T radioactivity at the gamma globulin region indicating formation of antibodies to thyroxine. On the other hand, in sera with a low thyroid antibody titre as in splenectomized monkeys or in those animals immunized within complete adjuvant, T-binding antibodies were not evident. It is concluded that removal of the spleen prior to thyroid isoimmunization in monkeys, rather than inhibiting the severity of the disease may even aid and abet immunopathogenic events destructive to the thyroid.
通过在甲状腺同种免疫之前切除四只猴子的脾脏,研究了脾脏在体液抗体形成及免疫性甲状腺炎发病机制中的作用。对脾切除动物以及完整对照动物进行了序贯免疫,并通过定期甲状腺活检以及在超过1年的时间里频繁检测体液抗体,来跟踪免疫疾病的进程。二级淋巴器官的切除显著抑制了凝集抗体反应,阻止了补体结合抗体的形成,但对甲状腺细胞毒性抗体没有影响。在完全佐剂中进行免疫的动物,在实验末期血清补体水平有明显下降趋势。尽管对某些免疫参数有抑制作用,但在甲状腺同种免疫之前对猴子进行脾切除并不干扰甲状腺病理过程的起始和进展。事实上,在用甲状腺加完全佐剂免疫的所有脾切除动物中,甲状腺出现纤维化病变(4+),甲状腺滤泡几乎消失,有些在初次免疫后120天就很明显;相比之下,完整动物尽管在340天内反复接受类似免疫程序,但仅出现非纤维化且不太严重的病变。在没有完全佐剂的情况下进行免疫,无论有无脾脏,均未诱发甲状腺病变。在所有有严重甲状腺病变的动物中,通过T和I-T树脂摄取测量显示甲状腺功能下降。对在完全佐剂中进行甲状腺同种免疫(并用I-T平衡后)的一只猴子的血清标本进行纸电泳,结果显示在γ球蛋白区域有明显的I-T放射性滞留,表明形成了甲状腺素抗体。另一方面,在脾切除猴子或在完全佐剂中免疫的动物中,甲状腺抗体滴度较低的血清中,未发现T结合抗体。结论是,在猴子甲状腺同种免疫之前切除脾脏,非但不会抑制疾病的严重程度,反而可能有助于甚至助长对甲状腺有破坏作用的免疫致病事件。