Rejection of marrow from DLA-identical canine littermates given transfusions before grafting: antigens involved are expressed on leukocytes and skin epithelial cells but not on platelets and red blood cells

Previous studies in dogs given 1200 R and a hemopoietic graft from DLA-identical littermates have shown that marrow graft rejection generally does not occur when the recipient is untransfused (58 of 59 achieved sustained engraftment) but is seen after a single transfusion of blood from the marrow donor on day -10 (13 of 18 rejected) and even after multiple transfusions of random blood (3 of 11 rejected). This study extends those initial observations by determining the incidence of rejection of DLA-identical littermate marrow grafts following administration of different cells from the marrow donor on days -24. -17. and -10 prior to transplantation. Using this protocol, the following results and conclusions were established. (1) All 19 dogs given transfusions of whole blood rejected their grafts. This 100% incidence of rejection after three transfusions indicates that more than one minor histocompatibility system outside of DLA is involved in transfusion-induced sensitization and subsequent marrow graft rejection. (2) Six dogs given subcutaneous injections of cultured skin epithelial cells rejected their subsequent marrow grafts. Hence, antigens mediating rejection are not restricted to hemopoietic cells but are also expressed on at least one other tissue. (3) Seven of 15 dogs given transfusions of platelet concentrates (“free” of white and red blood cells) rejected the marrow graft, while 8 showed sustained engraftment. (4) Five of 14 dogs given transfusions of red blood cells (free of white blood cells and platelets) rejected the marrow graft, while 9 had sustained engraftment. This suggests that only some (and perhaps none) of the non-DLA antigens responsible for rejection reside on platelets and red blood cells. To definitively answer this question, the current blood cell separation techniques must be improved further to provide pure red blood cells and platelets for transfusion studies. Assays of lymphocytotoxic antibodies, mixed leukocyte culture reactivity, and survival of donor platelets in the recipient did not predict the fate of the subsequent marrow graft. These findings in DLA-identical canine marrow graft recipients are of potential practical importance for planning platelet and red blood cell support of human marrow graft candidates.