Baboon Bone Marrow Transplantation in Humans: Application of Cross-Species Disease Resistance
We have generated murine antibody-facilitated (AF) bone marrow chimeras in the genetic combination P1----(P1 X P2)F1 by the simultaneous injection of P1 bone marrow cells and anti-P2 MHC monoclonal antibody into normal (unirradiated) adult (P1 X P2)F1 recipients. These mice have normal life spans and appear to be healthy, with no overt signs of graft-versus-host disease. We have undertaken an extensive survey of the ability of stable, long-term AF chimeras to generate immune responses in vitro and in vivo. Both T and B lymphocyte functions have been analyzed in proliferative and effector cell assays. The AF chimeras respond normally to mitogenic as well as antigenic stimuli, and exhibit normal capacities for cellular collaboration in the generation of immune responses. However, splenic lymphocytes from AF chimeras are substantially and specifically hyporesponsive or nonresponsive to host, P2-encoded, alloantigens in in vitro assays of cell-mediated immunity. This host-specific tolerance is exhibited by the cytotoxic T lymphocyte lineage; T helper cells necessary for the generation of a cytotoxic response may also have decreased reactivity to host determinants. We conclude that our protocol for the production of AF chimeras does not compromise the immune system of chimeric animals but does allow the maintenance of host-specific tolerance, after stable equilibrium has been attained.