AUTOIMMUNE SYNDROME AFTER INDUCTION OF NEONATAL TOLERANCE TO I-E ANTIGENS

Neonatal injection of semiallogeneic spleen cells induces a state of s pecific tolerance to the parental alloantigens, but also the developme nt of an autoimmune syndrome known as host-versus-graft disease (HVGD) . The autoimmune features are a consequence of the allogeneic cooperat ion between persisting alloreactive host T helper type 2 (T(H)2) cells and donor semiallogeneic B cells. It has been established that I-A al loantigens play a central role in the triggering of this HVGD. Here it was investigated if I-E antigens, which have shown functional differe nces, regarding autoimmunity and alloreactivity, with respect to I-A a ntigens, are also able to trigger this autoimmune syndrome. The inject ion of spleen cells from [B10.A(4R) x B10.A(2R)]F1 (I-E+) hybrid mice into newborn B10.A(4R) (I-E-) mice was accompanied by the establishmen t of chimerism and also by the development of a characteristic, but mo derated, HVGD. The weak intensity of this HVGD is likely due to the mo deration of the alloreactive responses induced against I-E molecules. Moreover, the marked increase in the levels of IgE and in the titers o f anti-DNA IgG1 antibodies strongly suggest that alloreactive T(H)2 ce lls play also a main role in the autoimmune syndrome following toleriz ation to I-E antigens. Therefore, it is concluded that the I-E and I-A isotypes are functionally similar with respect to the allogeneic cell ular interactions that account for the HVGD.