Developmental expression of autoimmune target antigens during organogenesis.

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.