Antileukemic effect of interleukin-2 on spontaneous development of leukemia after H-2-compatible allogenic bone marrow transplantation in AKR/J mice.
AKR/J mice, highly susceptible to spontaneous T cell leukemogenesis, were protected from developing the disease by H-2-compatible allogenic bone marrow transplantation (BMT) and intermittent treatment with interleukin-2(IL-2). Allogeneic BMT from C3H/HeJ mice and treatment with PBS yielded T cell leukemia in chimeras after the same latent period as that observed in normal AKR/J mice. In contrast, IL-2-treated chimeras caused an incidence of only 40% T cell leukemia. The preventing effect of IL-2 on leukemia development was not observed in one-year-treated chimeras, probably due to a lack of continuous antileukemic effects over the long term. Both LAK and NK activities in spleen cells were significantly increased in IL-2-treated chimeras. The cytotoxicity against T cell lymphoma cell line derived from AKR/J also increased in the IL-2-treated chimeras. Similarly, LPS-, PWM-, and IL-2-induced responses were increased in the IL-2-treated chimeras. TNF-alpha secretion from spleen cells also rose after IL-2-administration. IL-1 beta, IFN-gamma, and TNF-alpha mRNA became detectable in spleen cells using the PCR technique. The characteristics of leukemia cells in chimeras with overt leukemia were not directly affected by IL-2 administration. It is suggested that partial inhibition of spontaneous T cell leukemia development in AKR/J mice by allogeneic BMT and IL-2 may be due to the enhancement of graft-versus-leukemia effects. Further study may provide insights into the mechanisms involved in preventing leukemia development after allogenic BMT and IL-2 in AKR/J mice.
Hashino
S
S
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D016026:Bone Marrow Transplantation; D002678:Chimera; D016207:Cytokines / Q000378:metabolism; D006183:H-2 Antigens; D006648:Histocompatibility; D007376:Interleukin-2 / Q000627:therapeutic use*; D015458:Leukemia, T-Cell / Q000517:prevention & control*; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology; D014184:Transplantation, Homologous
D016207:Cytokines; D006183:H-2 Antigens; D007376:Interleukin-2