strontium-radioisotopes and Leukemia--Erythroblastic--Acute

Topics: Animals; B-Lymphocytes; Cell Transformation, Neoplastic; Erythropoiesis; Friend murine leukemia virus; Genes; Immune Tolerance; Immunity, Cellular; Immunity, Innate; Immunosuppression Therapy; Killer Cells, Natural; Leukemia, Erythroblastic, Acute; Lymphocyte Activation; Macrophages; Mice; Strontium Radioisotopes; T-Lymphocytes; T-Lymphocytes, Regulatory

The effector cells from non-immunized mice capable of lysing 51Cr-labelled FLD-3 BALB/c Friend virus-induced erythroleukemia cells in vitro and cells capable of clearing FLD-3 cells labelled with 5-iodo-2'-deoxyuridine-125I (125IdUrd) from the lungs in vivo were characterized and compared with natural killer (NK) cells reactive against YAC-I lymphoma cells. Unlike NK cells, the cells capable of lysing FLD-3 cells in vitro were insensitive to antibodies directed against NK-2.1 or Thy-1.2 antigens (plus complement) and to pretreatment of mice in vivo with silica particles, 89Sr or estradiol. Heat-killed C. parvum organism stimulated anti-FLD-3 effector cells without changing the slow rate (24 h) of lysis in vitro. The ability to clear FLD-3 and YAC-1 cells from the lung was normal and defective, respectively, in C57BL/6-bg/bg(beige) mice and in mice pretreated with 89Sr or estradiol. We conclude that natural cytotoxic (NC) cells lyse FLD-3 cells, Fv-2, which regulates resistance to leukemia induction by Friend virus, does not regulate NC(FLD-3) activity, and the virus does not affect NC(FLD-3) activity during the first several days of infection of normal genetically susceptible mice. However, infection of 89Sr-treated mice inhibits NC(FLD-3) function owing to the activation of suppressor cells. These data suggest (but do not prove) that effector cells similar or identical to NC(FLD-3) cells may function in vivo to resist the proliferation/survival of certain leukemia cells.

Topics: Animals; Cell Line; Cytotoxicity, Immunologic; Friend murine leukemia virus; Killer Cells, Natural; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; Lung; Mice; Mice, Inbred Strains; Strontium Radioisotopes

Treatment of mice with the long-lived bone-seeking radioisotope 89Sr results in the selective irradiation and destruction of the bone marrow. This is accompanied by a marked reduction in natural killer cell activity against YAC-1 lymphoma [NK(YAC-1)]. To test for the presence of cellular suppressors of NK(YAC-1) in 89Sr-treated mice, in vitro and in vivo cell mixture protocols were used. In vitro, we did not observe any specific inhibitory effect of spleen cells from 89Sr-treated mice on NK(YAC-1) activity of normal spleen cells. The NK(YAC-1) activity of 89Sr-treated mice, measured in vivo by their ability to clear radiolabeled YAC-1 cells from the lungs, was impaired. However, spleen cells from 89Sr-treated mice, when adoptively transferred with normal spleen cells, failed to inhibit the NK(YAC-1) activity of the latter in the lung clearance assay. Further, when normal spleen cells were injected into 89Sr-treated mice, the ability of the transferred cells to mediate in vivo activity was not suppressed in the 89Sr-treated host. These experiments support the suggestion that the low NK(YAC-1) activity in 89Sr-treated mice is not mediated by suppressor cells, but may be due to the destruction of the marrow microenvironment which is essential for the generation of functional NK(YAC-1) cells.

Topics: Animals; Cytotoxicity, Immunologic; Immunity, Cellular; Immunization, Passive; Leukemia, Erythroblastic, Acute; Lymphoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Spleen; Strontium Radioisotopes; T-Lymphocytes, Regulatory

The spontaneous regression of the erythroleukemia induced by the regressing Friend murine leukemia virus (F-MuLV) complex was inhibited by irradiation of the animals prior to F-MuLV inoculation. This inhibition was proportional to the dose of radiation used. Treatment of the mice with the bone-seeking isotope 89Sr also inhibited erythroleukemia regression, which implicates the same effector mechanisms involved in the resistance to F-MuLV or F-MuLV-induced immunosuprression. Erythroleukemias induced in athymic nude mice by the regressing F-MuLV complex exhibited higher rates of lethality than did the leukemias in heterozygous or homozygous thymus gland-containing controls. These data suggested the involvement of the immune system in erythroleukemia regression and the specific participation of thymus cells and an 89Sr-susceptible function, perhaps marrow-dependent cells, in the process of regression.

Topics: Animals; Friend murine leukemia virus; Immunity; Immunosuppression Therapy; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; Male; Mice; Mice, Nude; Neoplasm Regression, Spontaneous; Strontium Radioisotopes; Tumor Virus Infections

Friend leukemia virus suppresses the proliferative responses of normal thymus-dependent (T) and bursa equivalent-dependent (B) lymphocytes from spleen, thymus, lymph node, and bone marrow to mitogens. The suppressive effect of Friend virus complex (FV) requires fully infectious virions. Friend erythroleukemic cells, washed to removed extracellular virus, fail to suppress concanavalin A (Con-A)-induced mitogenesis of normal spleen cells. This indicates that FV does not mediate its immunosuppressive effect via transformed erythropoietic cells. The in vitro suppressive effect of FV on lymphocyte mitogenesis is under host genetic control. Spleen, bone marrow, and thymus cells from strains of mice susceptible to FV-induced leukemogenesis in vivo were quite susceptible to the suppressive effects of FV in vitro. On the other hand, similar cells from strains of mice such as C57BL/6 resistant to Friend erythroleukemia, were quite resistant to in virto immunosuppression by FV. Mitogenesis of splenic T cells from resistant B6 mice, previously treated with 89Sr, became susceptible to suppression by FV. This indicated that the in vitro resistance of lymphocytes to FV-induced suppression is not an intrinsic property of T cells, but is controlled by marrow-dependent (M) cells which are selectively eliminated by treatment with 89Sr. M-cell function does not develop in mice less than 3-wk old. The Con A response by thymus cells from 2-wk-old B6 mice was susceptible to suppression by FV, further supporting the concept that M cells may regulate the genetic resistance to FV.

Topics: Age Factors; Animals; B-Lymphocytes; Friend murine leukemia virus; Genes; Immunity, Cellular; Immunosuppression Therapy; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; Lymphocyte Activation; Macrophages; Male; Mice; Mice, Inbred Strains; Mitogens; Sarcoma, Experimental; Silicon Dioxide; Strontium Radioisotopes; T-Lymphocytes

Topics: Animals; Bone Marrow; Bone Marrow Cells; Cell Separation; Friend murine leukemia virus; Genes; Immunosuppression Therapy; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; Lymphocyte Activation; Lymphocytes; Macrophages; Mice; Mice, Inbred Strains; Species Specificity; Strontium Radioisotopes; T-Lymphocytes