Akashi T, Eishi Y
Department of Pathology, Tokyo Medical and Dental University, Japan.
Immunology. 1991 Nov;74(3):524-32.
A common factor existing among autoimmune target antigens was sought in association with their developmental expression during organogenesis. Autoimmunity against a certain organ was experimentally induced in rats by deliberate immunization with whole tissue extract of the respective organ. Histopathological changes in a target organ of the immunized rats were recorded, and tissue specificity of the raised autoantibodies was immunohistologically examined with tissue sections of normal adult rats. These immune sera were also reacted with tissue sections of a target organ in each stage of organogenesis, and the time of first expression of the target antigen was determined for each immune serum. As a result, induced autoantibodies were directed only to a limited number of tissue antigens, such as thyroid follicular antigens [gestation day 17 (17 GD)], salivary ductal antigens (18 GD), anterior pituitary antigens (21 GD), gastric parietal cell antigens (22 GD), neural myelin antigens (2 days after birth), retinal photo-receptor cell antigens (3 days after birth) and testicular germ cell antigens (4 weeks after birth). They were first expressed on the day indicated in parentheses. Comparing with the development of the immune system, which was monitored by demonstrating CD4- and/or CD8-positive cells in the developing thymus and spleen, a common feature of these potential autoimmune target antigens was found to be that they were expressed either in parallel with, or after, but never before, the development of the immune system. This observation might suggest why only a limited number of self antigens can be autoimmune target antigens among the enormously large number of antigen determinants existing in the whole extract of each organ.
研究人员探寻了自身免疫靶抗原之间存在的共同因素，以及它们在器官发生过程中的发育表达情况。通过用相应器官的全组织提取物对大鼠进行刻意免疫，在实验中诱导大鼠产生针对某一特定器官的自身免疫。记录免疫大鼠靶器官的组织病理学变化，并用正常成年大鼠的组织切片通过免疫组织化学方法检测所产生自身抗体的组织特异性。这些免疫血清还与器官发生各阶段靶器官的组织切片反应，确定每种免疫血清中靶抗原首次表达的时间。结果发现，诱导产生的自身抗体仅针对有限数量的组织抗原，如甲状腺滤泡抗原[妊娠第17天（17 GD）]、涎腺导管抗原（18 GD）、垂体前叶抗原（21 GD）、胃壁细胞抗原（22 GD）、神经髓鞘抗原（出生后2天）、视网膜光感受器细胞抗原（出生后3天）和睾丸生殖细胞抗原（出生后4周）。它们在括号中所示的日期首次表达。通过在发育中的胸腺和脾脏中显示CD4和/或CD8阳性细胞来监测免疫系统的发育，结果发现这些潜在的自身免疫靶抗原的一个共同特征是，它们要么与免疫系统的发育同时表达，要么在免疫系统发育之后表达，但从未在其之前表达。这一观察结果可能解释了为什么在每个器官的全提取物中存在的大量抗原决定簇中，只有有限数量的自身抗原能够成为自身免疫靶抗原。
