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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of in vitro-stimulated immune lymphocytes in tumor-bearing mice was studied. Spleen cells from BALB/c mice which had regressed Moloney murine sarcoma virus (M-MSV)-induced primary tumors, were sensitized in vitro by using Moloney murine leukemia virus-induced BALB/c lymphoma (LSTRA). Lymphocytes obtained 6 days after stimulation were examined for cytotoxic activity against LSTRA cells, labeled with 51 Cr or 99mTc, and inoculated into mice bearing MSv-induced primary tumors. The distribution of 52Cr-labeled lymphocytes was determined by counting the radioactivity of each organ. Compared to normal lymphocytes, in vitro-stimulated lymphocytes accumulated significantly in tumor tissues and lymphatic organs. The accumulation of MSV-immune lymphocytes in tumor tissues was not evident in 3-methylcholanthrene-induced BALB/c fibrosarcoma, suggesting the operation of specific mechanisms of accumulation of immune lymphocytes. Scintigraphy was performed by inoculating the 99mTc-labeled lymphocytes via the tail vein the tumor-bearing mice. Visualization of the tumor was possible in mice given in vitro-stimulated lymphocytes.
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PMID:Distribution of in vitro-stimulated immune lymphocytes in mice bearing Moloney murine sarcoma virus-induced primary tumor. 727 51

Spleen cells from 8-week-old, nonimmunized donor chickens can transfer resistance to a supralethal dose of the JMV leukemia line of Marek's disease (MD) to newly hatched, highly susceptible, histocompatible recipients. The population of cells transferring resistance has previously been shown to be non-T, non-B, and nonmacrophage in nature. We present data here showing that heavily x-irradiated spleen cells were unable to protect recipients from leukemia challenge. Both complement receptor-bearing and -lacking cells could confer resistance to newly hatched recipients. Fc receptor-bearing cells conferred significant protection to recipients, whereas spleen cells depleted of Fc receptor-bearing cells were unable to protect chickens from death after JMV challenge. This indicates that the population of spleen cells, which is moderately radiosensitive and which possesses Fc receptors, is responsible for the transfer of natural resistance to the malignancy in vivo.
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PMID:Transfer of natural resistance to Marek's disease (JMV) with nonimmune spleen cells. II. Further characterization of protecting cell population. 739 77

The HOX11 homeobox gene was identified via the translocation t(10;14) in T cell leukaemia. To determine the function of this gene in mice, null mutations were made using homologous recombination in ES cells to incorporate lacZ into the hox11 transcription unit. Production of beta-galactosidase from the recombinant hox11 allele in +/- mutants allowed identification of sites of hox11 expression which included the developing spleen. Newborn hox11 -/- mice exhibit asplenia. Spleen formation commences normally at E11.5 in hox11 -/- mutant embryos but the spleen anlage undergoes rapid and complete resorption between E12.5 and E13.5. Dying spleen cells exhibit molecular features of apoptosis, suggesting that programmed cell death is initiated at this stage of organ development in the absence of hox11 protein. Thus hox11 is not required to initiate spleen development but is essential for the survival of splenic precursors during organogenesis. This function for hox11 suggests that enhanced cell survival may result from the t(10;14) which activates HOX11 in T cell leukaemias, further strengthening the association between oncogene-induced cell survival and tumorigenesis.
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PMID:The Hox11 gene is essential for cell survival during spleen development. 755 17

Graft-versus-host disease (GVHD) due to allogeneic bone marrow transplantation can be prevented by depleting the T cells from the marrow graft in vitro. However, the elimination of the donor T cells results in a higher frequency of graft failure, secondary infections and, in case of leukaemia, relapse. We found, that, in contrast to normal spleen cells, spleen cells from A or B10 donor mice pretreated with xenogeneic antithymocyte serum (ATS) in vivo did not induce GVHD in non-irradiated (B10 x A)F1 hybrids. Spleen cells of ATS-pretreated A donors did not cause GVHD in allogeneic CBA mice made neonatally tolerant to the A donor strain either. Furthermore, spleen cells from ATS-treated donors did not cause GVHD in irradiated F1 hybrid recipients, moreover, they decreased the lethal effect of irradiation. The in vivo ATS pretreatment improved the repopulating capacity of spleen cells in irradiated syngeneic recipients, too. The effect of the ATS treatment does not rely solely upon the elimination of T cells, since flow cytofluorometric analysis revealed only a partial depletion of both the CD4+ and CD8+ T cells of the ATS-pretreated animals. These observations may also have clinical relevance.
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PMID:Spleen cells from antithymocyte serum pretreated mice do not induce GVHD but exert increased repopulating activity in irradiated semiallogeneic recipients. 787 94

A murine model for acute myeloid leukemia (mAML) was used to study graft-vs.-leukemia (GVL) effects on residual leukemic cells across both major (MHC) and minor histocompatibility antigens (mHA) barriers. In addition, the therapeutic effect of recombinant human interleukin-2 (rhIL-2)-administered postsyngeneic and allogeneic bone marrow transplantation (BMT) was examined. SJL/J mice inoculated with mAML cells were exposed later to total body irradiation (TBI) and transplanted with bone marrow cells (BMC) mixed with spleen cells derived from normal syngeneic (SJL/J), congenic (B10.S), or allogeneic (C57BL/6) donor mice. One-half of the mice in each group received low dose rhIL-2 for 3 days starting 1 day post-BMT. Spleen cells from treated recipients were transferred to secondary naive SJL/J mice for in vivo detection of residual tumor cells. At a tumor load of 10(5) cells per animal, none of the mice rescued with SJL/J or B10.S cells was cured since 100% of secondary recipients developed leukemia. Concomitant treatment of recipients of B10.S cells with rhIL-2 induced GVL effects since none of the secondary recipients developed leukemia after 2 years. All adoptive recipients of mice rescued with C57BL/6 cells remained free of leukemia after 2 years whether or not rhIL-2 was injected. The potency of the GVL effects observed across mHA and MHC were tumor-cell dose dependent since fewer animals inoculated with 10(6) mAML cells were cured. Only marginal GVL effects were noticed following syngeneic BMT and rhIL-2. Our results sustain the importance of the GVL effects in the treatment of myeloid leukemia and demonstrate that immunotherapy with rhIL-2 following BMT can enhance the therapeutic effect induced by the allograft.
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PMID:Enhancement of GVL effect with rhIL-2 following BMT in a murine model for acute myeloid leukemia in SJL/J mice. 787 38

Resistance and/or susceptibility for Friend leukemia virus (FLV)-induced leukemogenesis was examined in the fully H-2 incompatible C57BL/6 (B6)-->C3H radiation bone marrow chimeras (RBMC). The results indicated that B6-->C3H chimeras never developed FLV-induced leukemias when infected with FLV 4 months after bone marrow transplantation (BMT). Spleen cells from B6-->C3H chimeras that were preimmunized with 100 Gy-irradiated FBL-3 cells (FLV-induced leukemic cell line originated from B6 mice) were shown to generate anti-FBL-3 specific T-cell proliferation as well as cytotoxic T cells. We also found that when bone marrow cells from B6 mice were mixed with those from C3H mice and then grafted into supralethally irradiated C3H mice, resulting chimeras whose peripheral blood contained less than 30% C3H-derived (susceptible) cells were refractory to FLV-induced leukemogenesis. On the other hand, when C3H mice were infected with FLV and then supralethally irradiated 5 days later and grafted with bone marrow from B6 donors, they developed leukemias which were of B6 origin. Athymic nu/nu mice of B6 background were again shown to develop leukemia following infection with FLV. Possible implication of these findings on the role of T cell-mediated immune response in resistance to FLV-induced leukemogenesis and the immunocompetent nature of fully H-2 incompatible RBMC were discussed.
Leukemia 1993 Jul
PMID:Friend leukemia virus-induced leukemogenesis in fully H-2 incompatible C57BL/6-->C3H radiation bone marrow chimeras. 832 Oct 19

Spleen cells freshly isolated from normal mice were irradiated with 20 Gy X rays in culture. Northern blot hybridizations revealed that expression of the interleukin-1 beta (IL-1 beta) gene was induced immediately after irradiation and was increased for 2 h thereafter. Dibutyryl cyclic AMP also caused a persistent expression of the IL-1 beta gene, although it differed from X rays in that it coincidentally induced expression of the c-fos gene, which was not induced by X rays. Activation of either protein kinase C or calmodulin also induced early expression of both IL-1 beta and c-fos. Myeloid cells collected from the spleen of mice with granulocytic leukemia were X-irradiated in culture as above. The leukemia cells responded to X rays as well as to other stimuli in the same manner as the spleen cells, except that IL-1 beta mRNA was no longer detected 30 min after irradiation while c-fos was detectable for 2 h. When the leukemia cells were irradiated twice with a 3-h interval between irradiations, the second irradiation led to prolonged expression of IL-1 beta without inducing c-fos expression. These results suggest that ionizing radiation elicits early expression of the IL-1 beta gene through a mechanism that does not involve protein kinase C or A, or the transcription factor, c-fos. Whole-body irradiation of mice with 50 Gy 137Cs gamma rays also induced IL-1 beta expression in spleen but not in bone marrow or liver, although there was a delay of several hours before it was amply expressed. Furthermore, a delay as long as 24 or 72 h was observed when the radiation dose was reduced to 8.5 or 4 Gy. The results of this in vivo study suggest that the rapidity of expression of the IL-1 beta gene is dependent on the dose of radiation, and that the cells in the body cannot respond to radiation as rapidly as cells in culture.
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PMID:Induction of the expression of the interleukin-1 beta gene in mouse spleen by ionizing radiation. 838 62

Infection with the avirulent Fukaya strain of Toxoplasma gondii induced few inflammatory responses in the brain of C57BL/6 mice. When mice with chronic infection with the Fukaya strain were challenged with murine leukemia virus (MuLV) LP-BM5, which is known to induce a remarkable immunodeficiency in mice, those mice suffered from a severe encephalitis. Infiltration of mononuclear cells was remarkable in both meninges and parenchyma in those mice. Numerous sites of acute focal inflammation were noted in the brain and the presence of tachyzoites and Toxoplasma antigens was demonstrable in those areas by immunoperoxidase staining using rabbit anti-Toxoplasma IgG antibodies. All mice infected with both T. gondii and LP-BM5 MuLV died from 9 to 14 weeks after the virus infection, whereas no mice died in the infection with either T. gondii or the virus alone. Spleen cells from the mice with coinfection failed to respond to both T cell (Con A) and B cell mitogens (LPS) in vitro in contrast to the cells from mice infected with T. gondii alone that responded to those mitogens just as cells from normal mice did. Mice chronically infected with T. gondii and challenged with LP-BM5 MuLV appears to provide a good animal model of toxoplasmic encephalitis which is a major cause of morbidity and mortality in AIDS patients.
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PMID:Toxoplasma gondii: induction of toxoplasmic encephalitis in mice with chronic infection by inoculation of a murine leukemia virus inducing immunodeficiency. 838 26

The role of T helper 1 (Th1) and T helper 2 (Th2) responses in the murine acquired immunodeficiency syndrome (MAIDS) is unclear. It has been suggested that differential activation of T cell subsets, particularly a shift to Th2 cytokine production, may be associated with disease progression. To clarify the regulation of the cytokine network in the course of MAIDS, we examined the kinetics of cytokine production by isolated splenocytes. C57/BL6 mice were infected with the LP-BM5 mixture. The spleen cell proliferative response, together with IL-2, IFN-gamma, IL-10 and IL-4 production by unstimulated and ConA or anti-CD3 MoAb-stimulated spleen cells, were determined at various times after inoculation (weeks 1, 3, 6 and 9). Spleen cells isolated from murine leukemia virus complex (LP-BM5) infected mice spontaneously produced significant amounts of IL-2 and IFN-gamma one and three weeks post-infection, compared to uninfected controls. The capacity of isolated T cells to produce the Th1 cytokines IL-2 and IFN-gamma in response to stimulation with ConA and anti-CD3 MoAb decreased after 3 weeks of infection. The fall in IL-2 production ran parallel to the fall in the T cell proliferative response to ConA. IL-10 production in response to ConA and anti-CD3 MoAb increased after three weeks post-inoculation, and followed the reverse kinetic pattern to IFN-gamma and IL-2. In contrast, no significant spontaneous IL-4 production and no increase in IL-4 production in response to ConA or anti-CD3 MoAb occurred during the course of MAIDS, relative to uninfected controls. These results suggest that LP-BM5 infection leads to a fall in Th1 cytokine production rather than a clear switch to Th2 cytokine production.
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PMID:Kinetics of ex-vivo cytokine production by splenocytes during murine acquired immunodeficiency syndrome (MAIDS). 858 75

Met-ase-1 is a 30 000 Mr serine protease (granzyme) that was first isolated in the cytolytic granules of rat CD3(-) large granular lymphocytes. We screened a mouse genomic library with rat Met-ase-1 cDNA, and obtained bacteriophage clones that contained the mouse Met-ase-1 gene. The mouse Met-ase-1 gene comprises five exons spanning approximately 5.2 kilobases (kb) and exhibits a similar structural organization to its rat homologue and a family of neutrophil elastase-like serine proteases. Mouse Met-ase-1 mRNA was only detected in total cellular and poly A mRNA of mouse CD3(-) GM1(+) large granular lymphocytes derived from splenocytes stimulated with IL-2 and the mouse NK1.1(+) cell line 4 - 16. Spleen T-cell populations generated by Concanavalin A stimulation and a number of mouse pre-NK and T cell lines did not express mouse Met-ase-1 mRNA. The 5' flanking region of the mouse Met-ase-1 gene also shares considerable regions of identity with the 5' flanking region of the rat Met-ase-1 gene. A 3.3 kb segment of 5' sequence flanking the mouse Met-ase-1 gene was inserted upstream of the chloramphenicol acetyltransferase reporter gene and this construct transiently transfected into a variety of mouse and rat large granular lymphocyte leukemia and T-cell lines. The transcriptional activity of the mouse Met-ase-1 5' flanking region was significant in the RNK-16 large granular lymphocyte leukemia, strongest in the 4 - 16 mouse NK1.1(+) cell line, and weak in several mouse pre-NK cell lines. Reverse transcriptase polymerase chain reaction of mouse large granular lymphocyte mRNA was used to derive the full-length coding sequence for mouse Met-ase-1. The predicted hexapropeptide of mouse Met-ase-1 (Asn-6 to Gln-1), was deleted by polymerase chain reaction mutagenesis to enable expression of active mouse Met-ase-1 in mammalian COS-7 cells. Northern blot analysis and protease assays of transfected COS cell lysates against a panel of thiobenzyl ester substrates formally demonstrated that the mouse Met-ase-1 gene encodes a serine proteinase that hydrolyzes substrates containing a long narrow hydrophobic amino acids like methionine, norleucine, and leucine in the P1.
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PMID:Cloning and expression of the recombinant mouse natural killer cell granzyme Met-ase-1. 878 Nov 19


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