Autoimmune syndrome after induction of neonatal tolerance to I‐E antigens

Neonatal injection of semiallogeneic spleen cells induces a state of specific tolerance to the parental alloantigens, but also the development of an autoimmune syndrome known as host‐versus‐graft disease (HVGD). The autoimmune features are a consequence of the allogeneic cooperation between persisting alloreactive host T helper type 2 (TH2) cells and donor semiallogeneic B cells. It has been established that I‐A alloantigens play a central role in the triggering of this HVGD. Here it was investigated if I‐E antigens, which have shown functional differences, regarding autoimmunity and alloreactivity, with respect to I‐A antigens, are also able to trigger this autoimmune syndrome. The injection 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 establishment of chimerism and also by the development of a characteristic, but moderated, HVGD. The weak intensity of this HVGD is likely due to the moderation of the alloreactive responses induced against I‐E molecules. Moreover, the marked increase in the levels of IgE and in the titers of anti‐DNA IgGl antibodies strongly suggest that alloreactive TH2 cells play also a main role in the autoimmune syndrome following tolerization to I‐E antigens. Therefore, it is concluded that the I‐E and I‐A isotypes are functionally similar with respect to the allogeneic cellular interactions that account for the HVGD.