Analysis of peripheral immune tolerance uncovers a mouse strain-dependent in situ type of graft tolerance

We screened various mouse strains [C57BL/6, BALB/c, DBA/2, CBA/Ca, (CBAxC57 L/6)FI, SJL, C3H] for induction of peripheral immune tolerance. Only CBA/Ca mice treated with anti-CD4 + CD8 monoclonal antibodies and grafted with al logeneic skin showed long-term graft survival (150 to > 200 days). Interest ingly, T cells from the tolerant CBA/Ca mice rejected bone marrow/spleen ce lls of the skin graft donor strain and caused lethal graft-versus-host dise ase when transplanted to the donor strain. Furthermore, peripheral toleranc e was easily broken: CBA/Ca mice could be reactivated to reject their toler ated grafts via immunization with (graft donor x recipient strain)F1 bone m arrow cells. Thus, in contrast to the generalized nature of central toleran ce, our experiments show that peripheral immune tolerance is strain depende nt and locally restricted to graft tissue.