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

In our laboratory, we have developed a murine model to examine GVHD across minor histocompatibility antigens. In our model, GVHD is induced by injecting B10.D2 spleen cells into irradiated BALB/c recipients. Seven to 10 days after irradiation and injection of cells, there are significant changes in cell function in the recipient spleens. In the B10.D2----BALB/c (600 rad) model, recipient spleen cells are profoundly unresponsive to Con A and LPS stimulation but show increased B cell activity measured by Staphylococcus aureus protein A plaque-forming activity. Spleen cells from such GVH mice profoundly suppress the mitogenic responses of normal BALB/c or B10.D2 spleen cells to Con A and LPS. The degree of impairment of the mitogenic response and the ability to suppress normal cells is proportional to the dose of cells used to induce GVH reactions. Both the inability to respond to mitogens and the capacity to suppress are also related to the dose of irradiation given to the recipients. In addition, immunosuppression across minor histocompatibility antigens shows an unevenhandedness. If we inject parental B10.D2 or BALB/c cells into F1 recipients (P----F1), there is greater inhibition of mitogenic responses when B10.D2 parental cells are given than when BALB/c cells are given to the irradiated F1 recipients. These experiments show that significant immunosuppression occurs during GVH reactions across minor histocompatibility barriers. The degree of suppression varies according to the dose of cells used to induce GVH, the dose of irradiation to the recipient and the "strength" of the GVH recognition system. Such experiments provide models for GVH disease seen in humans who receive treatment for leukemia or other diseases that involves recipient irradiation and infusion of HLA-identical bone marrow.
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PMID:Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. I. Impairment of mitogen responses and suppressor phenomena. 315 67

The B-cell differentiation-inducing activity of interleukin-1 (IL-1) was compared with that of T-cell replacing factor (TRF)/interleukin-5 (IL-5), which was originally described as a late-acting B-cell differentiation-inducing factor. Human recombinant IL-1 and murine recombinant TRF/IL-5 were used in this study. Purified B cells from non-primed or antigen-primed mice, LPS-stimulated B-cell blasts, and chronic B-cell leukaemia (BCL1) cells were used as the responding B-cell population. Addition of IL-1 to the culture of normal B-cells and sheep red blood cells (SRBC) induced a dose-dependent anti-SRBC IgM response, with maximal response at 100 U/ml, whereas the response induced by TRF/IL-5 was less than that induced by IL-1 and did not reach the maximum even at 100 U/ml. Addition of anti-IL-1 antibody, but not anti-TRF/IL-5 antibody or anti-IL-2 receptor antibody, inhibited IL-1-induced anti-SRBC responses. Depletion of cells adherent to Sephadex beads from splenic B cells showed no significant effect on the magnitude of the total responses. IL-1 could induce little, if any, differentiation in antigen-primed B cells, LPS-stimulated B-cell blasts, or BCL1 cells into antibody-secreting cells, whereas differentiation could be induced by low doses of TRF/IL-5 (1-2 U/ml). Of great interest is that suboptimal doses of IL-1 (10 U/ml) could synergize with TRF in the primary anti-SRBC PFC responses. Kinetic studies revealed that IL-1 acts on B cells for the first 2 days and TRF/IL-5 for the last 3 days in 5-day cultures of B cells. These results suggest that IL-1 acts primarily on resting B cells as a differentiation-inducing factor in the presence of antigen, and also acts as a 'priming' factor for TRF/IL-5.
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PMID:Role of recombinant interleukin-1 compared to recombinant T-cell replacing factor/interleukin-5 in B-cell differentiation. 328 Apr 72

We have examined the effect of tumor-promoting phorbol esters such as phorbol myristate acetate (PMA) on the murine B cell leukemia BCL-1 and its in vitro adapted derivative CW.13.20. Phorbol esters, including PMA and phorbol dibutyrate (PDBu), were potent inhibitors of BCL-1 IgM secretion induced by either LPS or lymphokines; half-maximal inhibition was obtained with 0.1 nM PMA and 0.8 nm PDBu. The inhibitory action of PDBu on BCL-1 cells was reversible for over 1 hr, but after 5 hr 70% of the inhibition was irreversible. Irreversible inhibition could be blocked by cycloheximide, suggesting a requirement for protein synthesis. The specificity of PDBu inhibition was examined by comparing the patterns of protein synthesis in PDBu-treated and control BCL-1 cells. Total incorporation of [35S]methionine into protein by BCL-1 cells cultured in the presence of PDBu was similar to that of untreated cells. Analysis of radiolabeled proteins by SDS-PAGE and autoradiography revealed no consistent changes in the pattern of protein synthesis except at those positions corresponding to the heavy and light chains of IgM. Immunoprecipitation with an affinity-purified anti-IgM indicated that PDBu inhibited the increased synthesis of heavy and light chain that follows stimulation by lymphokine but did not diminish control IgM synthesis. Induced IgM secretion from CW.13.20 cells was also inhibited by phorbol esters, indicating a direct action on B cells. Delaying the addition of phorbol ester relative to lymphokine or LPS by 24 hr significantly reduced inhibition of induced IgM secretion from both BCL-1 and CW.13.20 cells. This suggests that phorbol esters specifically interfere with the signal for induction of IgM secretion by both lymphokine and LPS.
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PMID:Phorbol esters specifically inhibit induction of immunoglobulin secretion in a murine B cell leukemia. 387 17

Murine peritoneal macrophages elicited by dimethyldioctadecylammonium bromide (DDA), which is a potent immunologic adjuvant, were examined for cytotoxic and growth inhibiting activity for malignant cells. DDA macrophages had no cytolytic activity for murine B16BL-6 melanoma or human SMS-SB pre-B leukemia cells even in the presence of up to 1 microgram bacterial endotoxin (lipopolysaccharide, LPS)/ml. However, they exhibited a variable inhibitory effect on the growth of several lines of leukemia cells. The number of SMS-SB and human NALL cells remained essentially static in the presence of DDA macrophages while they increased significantly when cultured with resident macrophages. In contrast, L1210 cells increased 5-8-fold in the presence of macrophages elicited either by DDA or the inflammatory agent proteose peptone (PP). Although DDA macrophages retarded L1210 growth relative to PP macrophages, both populations responded to LPS in a comparable dose dependent manner to become essentially cytostatic at 1 microgram LPS/ml.
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PMID:Effect of dimethyldioctadecylammonium bromide induced macrophages on malignant cell proliferation. 400 32

When BALB/c mice were first infected with Rauscher murine leukemia virus (MuLV-R) and then superinfected with Herpes simplex virus type 2 (HSV-2) the inhibition of the evolution of splenomegaly was observed. The effect did not depend on the route of HSV-2 administration. Experiments in which potent anti-interferon serum was administered to double infected mice suggested that the antagonism between MuLV-R and HSV-2 was not mediated by endogenous interferon, HSV-2 was found to replicate in the LPS stimulated spleen cells which are also target cells for MuLV-R; this suggested that the intrinsic interference between both viruses could take place. Mice with Rauscher virus induced disease were found to be more susceptible to infection with Herpesviruses than normal mice.
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PMID:Double infection of BALB/c mice with Rauscher murine leukemia and Herpes simplex virus type 2. 625 90

LPS-stimulated leukemia cells derived from BALB/c mice bearing transplantable B-lymphocytic leukemia (BCL1) which arose spontaneously in a female BALB/c mouse, contained viral particles as suggested by electron microscopy as well as by tissue cultures using the XC assay. Some cell free extracts prepared from BCL1 cells were capable of transforming normal B-lymphocytes when inoculated into untreated syngeneic recipients. Cytogenetic analysis of spleen cells obtained from a splenomegalic male mouse neonatally inoculated with cell-free extract indicated that the tumor cells had a male karyotype with 42 chromosomes as compared to 37 chromosomes and a female karyotype in original BCL1 cells, thus excluding the possibility of tumor propagation by transplantation of intact BCL1 cells. These findings suggest viral involvement in the etiology of BCL1.
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PMID:Demonstration and characterization of virus released by murine B cell leukemia cells (BCL1). 633 65

The permissiveness of normal splenic lymphocytes to Friend murine leukemia virus was determined by enumeration of cells producing infectious MuLV following infection with Friend virus in vitro. The infection was enhanced greatly in the presence of mitogens in the culture medium. The number of infected cells in cultures stimulated with bacterial lipopolysaccharide increased progressively between days 1 and 7 whereas in cultures with concavalin A, the number of infected cells reached a maximum on days 3-4 post infection and then declined to the level observed in unstimulated cultures. The con-A-enhanced infection was absent in cultures of splenocytes from nude mice but was present in cultures from nude mice implanted with thymus glands 6 weeks or more before use as donors of spleen cells. The cells permissive to MuLV upon con-A stimulation segregated in the nylon-wool-adherent fraction (together with B cells involved in the LPS-dependent infection) whereas the nylon-non-adherent fraction, containing approximately 90% T cells, was refractory to in vitro infection. The con-A-dependent infectious centers were inhibited by cytotoxic treatment with anti-Thy 1.2 antibody plus complement. These results indicate the existence of two subpopulations of splenic T cells, a major nylon-non-adherent and a minor, nylon-adherent subpopulation, which are, respectively, non-permissive and permissive to MuLV-Friend.
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PMID:Target cell heterogeneity in murine leukemia virus infection. II. Demonstration of Friend leukemia-virus-permissive and non-permissive subsets of splenic T cells. 697 39

Murine lymphocytes cultured with frozen and thawed Rauscher murine leukemia virus 100,000 x G supernatants demonstrated increased 3H-thymidine uptake. The stimulatory capacity co-purified with the major envelope glycoprotein, gp70, and can be specifically removed from viral supernatants by absorption with anti-gp70 antibody-linked Sepharose. Cells from all strains tested, including strains prone to autoimmune disease (MRL/1, (NZB X W)F1, NZB, and BXSB), immunologically normal strains (DBA/2, C57B1/6, BALB/c, C3H and 129/J), genetic low responders to LPS (C3H/HeJ), and mice congenitally T cell deficient (BALB/Wehi nu/nu) were equivalently responsive to viral protein stimulation. The response peaked after 3 to 4 days of culture, and cells responded at that time after brief exposure to virus supernatants at the initiation of culture. When gp70 concentrations comparable to serum levels were used, both spleen and mesenteric lymph node cells were capable of responding with stimulation indices of between 5 and 10; whereas bone marrow cells responded poorly, and neither thymocytes nor cortisone-resistant thymocytes responded. Lymphocyte stimulation was not diminished by the depletion of adherent cells, and both T- and B cell-enriched populations responded.
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PMID:Stimulation of murine lymphocytes by Rauscher leukemia virus in vitro. 735 Feb 33

A number of recent studies has shown that animals immunized with cytokine secreting primary tumors show resistance against an unmodified tumor cell challenge. In the present study we have evaluated the potential role of IL6, a myeloid differentiation inducing factor, in modifying myeloid leukemia cells, a tumor so far not challenged by this approach. M1 cells transduced with N2 based retrovirus carrying the murine IL6 gene exhibit morphological and functional alterations. Genetically modified M1 cells show significant reduction in the growth constant coefficient and in the ability to form hematopoietic colonies. Flow cytometry analysis demonstrate increased expression of CD11b, CD18, F4/80, FcR and MHC class II, suggesting driven differentiation towards commitment. Transduced cells secrete high level of autocrine IL6 and, upon activation with LPS, high levels of TNF further indicating a functional alteration and differentiation. The insertion of IL6 gene coding for signals of cell activation and improved expression of MHC antigens into myeloid leukemia cells may enable more effective tumor recognition in vivo, and boost the local as well as the systemic immune-mediated anti-leukemia response.
Leukemia 1995 Oct
PMID:Modification of M1 cells by exogenous introduction of IL6 gene: a model for gene therapy of acute and chronic myeloid leukemia in mice. 747 25

To examine the region critical for differentiation in the human IL-4 receptor (hIL-4R), we transfected the Abelson murine leukemia virus (A-MuLV)-transformed murine pre-B cell line A20 with plasmid DNA encoding the hIL-4R. Transfectants expressed high affinity hIL-4Rs on the cell surface. Treatment with LPS and hIL-4 induced germline C epsilon transcripts in hIL-4R expressing A20 cells. Several hIL-4R mutant plasmids were then transfected into A20 cells and the transfectants were examined for hIL-4R expression and the ability to induce germline C epsilon transcripts upon stimulation with LPS and hIL-4. Although all A20 transfectants tested expressed the high-affinity hIL-4R, A20 transfectants expressing the mutant hIL-4R, which contains only 8 amino acids in the cytoplasmic domain, did not respond to LPS and hIL-4 with germline C epsilon transcripts. In addition, A20 transfectants expressing an internally deleted hIL-4R, in which the deleted region has been identified as the critical region for growth signal transduction in the previous study, failed to induce germline C epsilon transcripts with LPS and hIL-4. These results indicate that the critical region for the differentiation signal in the hIL-4R is identical to that for the growth signal, suggesting that IL-4 may share, at least partly, a common signal pathway for both growth and differentiation.
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PMID:The critical region in the cytoplasmic domain of human IL-4 receptor for induction of IgE synthesis. 759 Sep 38


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