Spontaneous and IL-2-induced anti-leukemic and anti-host effects against tumor- and host-specific alloantigens.
The graft-vs-leukemia (GVL) effect and its connection to graft-vs-host disease (GVHD) were studied in F1 hybrid mice after parental bone marrow transplantation. (BALB/c x C57BL/6) F1 mice (F1) were sublethally and lethally irradiated and inoculated with 10(4) BCL1 cells, a murine leukemia of BALB/c (BALB) origin. Subsequently mice were transplanted with F1 (syngeneic), BALB (allogeneic to the host but syngeneic to the tumor), C57BL/6 (B6) (allogeneic to both host and tumor) spleen cells, or spleen cells mixed with syngeneic (F1) bone marrow cells, respectively. Fresh BALB (H-2d) and B6 (H-2b) spleen cells, which induce equally strong GVHD in the F1 recipient against H-2b and H-2d alloantigens, respectively, were assayed for their ability to induce GVL effects on BCL1 (H-2d) cells with and without in vivo administration of human rIL-2. In order to increase the GVL effects, spleen cells were incubated for 4 days with rIL-2 to generate IL-2-activated killer cells. The results of adoptive transfer experiments showed that only immunocompetent B6 cells led to consistent eradication of leukemia. Neither BALB nor syngeneic F1 cells induced curative GVL effects regardless of whether spleen cells were further stimulated with rIL-2 in vitro, in vivo, or both. Our data support the theory that GVL effects are caused by T cell-dependent immune responses of allogeneic T cells and not by MHC-nonrestricted NK or rIL-2-activated NK cells, independently of the GVHD process itself. Hence, recognition and killing of tumor cells is most probably a MHC-restricted T cell-dependent process.
Cohen
P
P
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Vourka-Karussis
U
U
Weiss
L
L
Slavin
S
S
D000818:Animals; D016026:Bone Marrow Transplantation; D006086:Graft vs Host Disease / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014916:Whole-Body Irradiation
D006183:H-2 Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins