The role of natural suppressor and natural killer activities in resistance to hemopoietic transplantation in unirradiated hosts.
We report here that bone marrow stem cell engraftment in unirradiated hosts correlates with levels of natural suppressor (NS) activity in the host at the time of transplantation. This is shown in the antibody-facilitated murine chimeras, in which conditioning consists of a single injection of anti-host MHC antibody, which results in long term hemopoietic engraftment in P----F1 and syngeneic donor-host combinations. The data establish that, in two independent situations, engraftment is reduced in hosts with elevated NS activity. Resistance to engraftment in antibody-conditioned adult hosts is increased by prior administration of CFA, which also increases NS activity. Likewise, neonatal animals, which are highly resistant to antibody-facilitated engraftment, exhibit a spontaneously-increased level of NS activity. This resistance declines with the ontogenic waning of splenic NS activity. Conversely, administration of facilitating antibody decreases host bone marrow NS activity, while anti-MHC antibodies that fail to facilitate engraftment do not reduce it. NK activity, on the other hand, correlates poorly with resistance or susceptibility to marrow engraftment in these situations. These results suggest that immunoregulatory functions associated with hemopoiesis may control engraftment of donor stem cells in unirradiated hosts.
Sadelain
M W
MW
Department of Immunology, University of Alberta, Edmonton, Canada.
Voralia
M
M
Green
D R
DR
Wegmann
T G
TG
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D003433:Crosses, Genetic; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011292:Premedication; D013154:Spleen; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000961:Antilymphocyte Serum; D005620:Freund's Adjuvant