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

ABSTRACT

We screened various mouse strains [C57BL/6, BALB/c, DBA/2, CBA/Ca, (CBAxC57L/6)F1, SJL, C3H] for induction of peripheral immune tolerance. Only CBA/Ca mice treated with anti-CD4 + CD8 monoclonal antibodies and grafted with allogeneic skin showed long-term graft survival (150 to >200 days). Interestingly, T cells from the tolerant CBA/Ca mice rejected bone marrow/spleen cells of the skin graft donor strain and caused lethal graft-versus-host disease when transplanted to the donor strain. Furthermore, peripheral tolerance was easily broken CBA/Ca mice could be reactivated to reject their tolerated grafts via immunization with (graft donor x recipient strain)F1 bone marrow cells. Thus, in contrast to the generalized nature of central tolerance, our experiments show that peripheral immune tolerance is strain dependent and locally restricted to graft tissue.