Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+,2- T cells. Tumor eradication does not require participation of cytotoxic T cells.
The ability of noncytolytic Lyt-1+,2- T cells immune to FBL-3 leukemia to effect eradication of disseminated FBL-3 was studied. Adult thymectomized, irradiated, and T-depleted bone marrow-reconstituted (ATXBM) B6 hosts were cured of disseminated FBL-3 by treatment with 180 mg/kg cyclophosphamide (CY) and adoptively transferred Lyt-1+,2- T cells obtained from congenic B6/Thy-1.1 donors immune to FBL-3. Analysis of the T cell compartment of ATXBM hosts treated and rendered tumor-free by this therapy revealed that the only T cells present in the mice were donor-derived Lyt-1+,2- T cells. In vitro stimulation of these T cells with FBL-3 tumor cells, which express class I but no class II major histocompatibility complex antigens, induced lymphokine secretion, but did not result in the generation of cytotoxic T lymphocytes (CTL). Thus, in a setting in which mice lack Lyt-2+ T cells, and in which no CTL of either host or donor origin could be detected, immune Lyt-1+,2- T cells, in conjunction with CY, mediated eradication of a disseminated leukemia. The results suggest that delayed-type hypersensitivity responses induced by immune T cells represent a potentially useful effector mechanism for in vivo elimination of disseminated tumor cells.
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007116:Immunization, Passive / Q000379:methods*; D007371:Interferon-gamma / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation
D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D003520:Cyclophosphamide