Treatment of disseminated leukemia with cyclophosphamide and immune cells: tumor immunity reflects long-term persistence of tumor-specific donor T cells.
B6 mice bearing disseminated syngeneic FBL leukemia can be cured by treatment on day 5 with 180 mg/kg cyclophosphamide and 2 x 10(7) adoptively transferred syngeneic immune spleen cells. Complete tumor eradication in this model requires more than 30 days and is dependent upon the transfer of specifically immune T cells. To evaluate the relative contributions of host and donor T cells to tumor elimination and the maintenance of tumor immunity, donor cells obtained from Thy congenic mice were used for adoptive transfer. Thus, host and donor T cells could be readily distinguished by the expression of either Thy-1.2 or Thy-1.1 antigen. The results demonstrated that the majority of immunologically competent T cells present in hosts cured by adoptive therapy were of host origin. A small population of donor T cells, however, persisted long after transfer. At day 60, a time point shortly after tumor eradication had been completed, 5% of splenic T cells were of donor origin, and by day 120 this percentage had decreased to less than 2%. Functional studies performed at both time points revealed that this small number of residual donor T cells contained the subpopulation of tumor-reactive T cells present in the host. Thus, host T cells did not make a substantial contribution to the expression of the anti-tumor response and presumably have little role in either tumor eradication or the long-term maintenance of tumor immunity.
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005434:Flow Cytometry; D007111:Immunity, Cellular; D007116:Immunization, Passive; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000637:transplantation*; D018800:Thy-1 Antigens; D013997:Time Factors
D000954:Antigens, Surface; D018800:Thy-1 Antigens; D003520:Cyclophosphamide