AUTOIMMUNITY FOLLOWING NEONATAL TOLERANCE TO ALLOANTIGENS - ROLE OF DONOR I-A AND I-E MOLECULES

The injection of semi-allogeneic F1 spleen cells into newborn mice of a parental strain induces a state of immune tolerance characterized by anti-donor CTL unresponsiveness and the appearance of a transient SLE -like autoimmune syndrome associating autoantibody production, hyperga mmaglobulinemia, splenomegaly and glomerulonephritis. Our previous exp eriments have demonstrated that host Th2-like CD4(+) T lymphocytes act ivate donor F-1 B cells persisting in the host to produce autoantibodi es, and that this cellular interaction relies on the presence of alloM HC class II molecules on donor B cells. In order to investigate the ro le and the involvement of MHC alloantigens in the cellular T(host)-B(d onor) interaction, newborn C57BL/6 (B6) mice were injected with F-1 sp leen cells differing from the host at the level of defined portions of the MHC class I (K) or class II (I-A and I-E) molecules. B6 mice inje cted at birth with spleen cells from different F-1 strains were tolera nt to each alloantigen (alloAg) tested, as assessed by specific anti-d onor CTL unresponsiveness. However, the SLE-like autoimmune syndrome o nly developed in B6 mice injected at birth with F-1 spleen cells diffe ring at the level of MHC class II I-A of I-E molecules. Autoantibodies appeared later in B6 mice neonatally tolerized to I-E alloAg than tho se detected in B6 mice neonatally tolerized to I-A alloAg. These resul ts show that the SLE-like autoimmune disease that develops concomitant ly to neonatally-induced tolerance to alloAg is the consequence of cog nate T host-B donor cellular interactions triggered by even minute dif ferences in the MHC class II I-A or MHC class II I-E molecules.