Graft versus leukemia. VIII. Selective reduction in antihost reactivity without loss of antileukemic reactivity by treatment of donor mice with lipopolysaccharide.
Spleen and lymph node cells from DBA/2 (H-2d) donor mice treated with multiple injections of bacterial lipopolysaccharide (LPS) were tested in vivo for reactivity against normal tissues of host AKR (H-2k) mice against an AKR long-passage, acute lymphoblastic leukemia (BW5147). LPS treatment of donor mice resulted in a reduction in graft-versus-host (GVH) reactivity without loss of graft-versus-leukemia (GVL) reactivity. Immunocompetent cells from LPS treated DBA/2 donors were effective when used for adoptive immunotherapy (in combination with chemoradiotherapy) of BW5147 leukemia. GVH associated mortality decreased as the dose of spleen cells from LPS treated histoincompatible donors was increased as much as four times the number necessary to eliminate leukemia. The mechanism by which LPS reduced GVH reactivity without eliminating GVL reactivity is unclear; however, it does not appear to be the result of a dilution in the number of GVH reactive cells by nonlymphoid elements in the donor spleen nor of the adjuvant effects of LPS on resistance to bacterial infections.
D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use; D006087:Graft vs Host Reaction / Q000187:drug effects*; D007165:Immunosuppression Therapy; D007942:Leukemia, Experimental / Q000276:immunology / Q000401:mortality / Q000628:therapy; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000637:transplantation; D014184:Transplantation, Homologous
D008070:Lipopolysaccharides; D003520:Cyclophosphamide