A T cell receptor transgenic model of severe, spontaneous organ-specific autoimmunity

The, development of mouse models of human organ-specific autoimmune disease s has been hampered by the need to immunize mice with autoantigens in poten t adjuvants. Even autoantigen-specific T cell receptor transgenic models of autoimmunity have proven to be complex as the transgenic mice frequently f air to develop disease spontaneously. We have isolated a CD4(+) T cell clon e (TxA23) that recognizes the gastric parietal cell antigen, H/K ATPase alp ha -chain(630-641), from a mouse with autoimmune gastritis that developed a fter thymectomy on day 3 of life. The T cell receptor alpha and beta genes from this clone were used to generate A23 transgenic mice. All A23 transgen ic animals spontaneously developed severe autoimmune gastritis, and evidenc e of disease was detected as early as day 10 of life. Gastritis could be tr ansferred to immunocompromised mice with a limited number of transgenic thy mocytes (10(3)), but as many as 10(7) induced only mild disease in wild-typ e animals. Due to the complete penetrance of spontaneous disease, identity of the auto-antigen, susceptibility to immunoregulation, and close relation to autoimmune gastritis in man, A23 transgenic mice represent a unique CD4 (+) T cell-mediated disease model far understanding the multiple factors re gulating organ-specific autoimmunity.