ACUTE GRAFT-VERSUS-HOST REACTION IN SCID MICE LEADS TO AN ABNORMAL EXPANSION OF CD8(-BETA-14(+) AND A BROAD INACTIVATION OF DONOR T-CELLS FOLLOWED BY A HOST-RESTRICTED TOLERANCE AND A NORMALIZATION OF THE TCR V-BETA REPERTOIRE IN THE CHRONIC PHASE()V)

The persistence and selection of allogeneic CBA/J T lymphocytes were s tudied during graft-versus-host (GVH) reaction in immunodeficient C.B- 17 SCID (SCID) mice. After neonatal injection the donor cells primaril y migrated to the spleen plus lymph nodes (SL) and the thymus of the r ecipients. Thirteen days post engraftment, CD8(+) cells in SL had incr eased five times in cell number with an 18-fold increase of CD8(+)V be ta 14(+) cells, paralleled by clinical signs of GVH disease (GVHD). Do nor lymphocytes from these mice were proliferative unresponsive to all ogeneic Balb/c or C57B1/6 SL cells, whereas 8 weeks post injection the tolerance was confined to H-2(d) specific donor cells. Here, spleens had a total cell content similar to untreated SCID mice but the averag e percentage of donor cells had reached 25%. Moreover, the CD4/CD8 cel l ratio in the donor population in SL and thymus had changed to normal and the TCR V beta repertoire was similar to that of the originally i njected cells. Following secondary transfer into syngeneic CBA/Ca nu/n u recipients donor cells regained a significant but reduced response t o H-2(d) stimulators indicating that the antigen specific tolerance of allogeneic donor cells in the SCID mice was due, at least in part, to a reversible state of anergy.