RECIPIENT-SPECIFIC DONOR CYTOTOXIC T-LYMPHOCYTES ENHANCE ENGRAFTMENT OF UNRELATED, DLA NONIDENTICAL CANINE MARROW

Resistance to canine marrow grafts from unrelated DLA non-identical do nors can be overcome by infusion of viable donor peripheral blood leuk ocytes or thoracic duct cells in addition to the marrow. The mechanism s by which these cells enhance engraftment are unknown but are likely to include a graft-versus-host reaction. The current study investigate d whether recipient-specific, donor alloreactive cytotoxic lymphocytes mediating a graft-versus-host reaction could abrogate resistance to c anine marrow grafts. To this purpose, cytotoxic donor lymphocytes (CTL ) specific for recipient DLA antigens were generated in vitro and expa nded in culture by exogenous interleukin-2 (IL-2). Two groups of dogs were studied. All were given 9.2 Gy total body irradiation followed by 3.7 X 10(8) marrow cells/kg from an unrelated DLA non-identical donor on day 0 and 1.2 x 10(8) host-specific CTL/kg on days 1 and 2. Dogs i n group 2 were given, in addition, subcutaneous injections of recombin ant human IL-2, 10 000 U/kg twice daily on days 1 through 10 post-graf ting. Ten of 16 dogs in the two groups showed hematopoietic engraftmen t regardless of whether they received in vivo IL-2. Engraftment in cur rent dogs was significantly better than that in 47 controls given marr ow alone (p = 0.001), although it was worse than that in 64 dogs given marrow and an order of magnitude higher number of viable mononuclear cells obtained from the peripheral blood (p = 0.007). Findings are con sistent with the hypothesis that infused donor T lymphocytes enhance e ngraftment through a graft-versus-host effect directed against radiati on-resistant immunologically active host cells, thus overcoming resist ance to unrelated marrow grafts.d