Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BCL1, a spontaneous B cell leukemia of BALB/c origin, is rejected by C.B-20 (Ighb, H-40b) but not BALB/c (Igha, H-40a) mice. Adoptive transfer of C.B-20 anti-BCL1 effector cells specific for the minor histocompatibility Ag H-40a protects irradiated C.B-20 but not BALB/c recipients. Because C.B-20 donor cells could potentially generate graft-vs-host disease (GVHD) in BALB/c recipients, we investigated the possibility that GVHD prevents the anti-tumor effect. GVHD was induced in (C.B-20 X B10.D2)F1 [H-2d, H-40b X H-2d,H-40b] recipients after injection of B10.D2-primed C.B-20 donor cells. GVHD was indicated by the histologic appearance of tissue sections from C.B-20----F1 livers, target organs of GVHD, which showed a marked mononuclear cell infiltrate around the portal tracts and central veins. In addition, splenic lymphocytes from these mice had altered CD4/CD8 ratios and were unable to respond to the polyclonal activators Con A and LPS. The mitogen unresponsiveness was at least partially due to the presence of a suppressor cell, because proliferation of normal spleen cells to Con A and LPS was suppressed upon addition of C.B-20----F1 spleen cells. Further immune dysfunction was evident by the inability of T cells from mice with GVHD to generate a CTL response to H-2 alloantigens. Addition of C.B-20----F1 spleen cells to F1 responder cells at the induction of culture did not prevent generation of CTL, indicating that a suppressor cell was not responsible for the lack of CTL activity. In this setting of GVHD, F1 recipients were able to reject BCL1 upon adoptive transfer of C.B-20 anti-BCL1 effector cells. These data indicate that GVHD-induced immune dysfunction does not inhibit the activity of antileukemia T cells.
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PMID:Effect of graft-versus-host disease on anti-tumor immunity. 196 93

(B10.A x A/WySn)F1, H-2a/a, mice are genetic nonresponders to the envelope protein of Friend murine leukemia helper virus (F-MuLV) when immunized with a recombinant vaccinia virus expressing F-MuLV env gene. In contrast these mice can be protectively immunized against leukemogenic Friend virus complex using formalin-fixed F-MuLV virions in CFA. To determine which viral proteins were responsible for this immune protection, virion proteins prepared by SDS-PAGE and electroelution were used to immunize mice. Purified gp70 envelope protein in CFA was capable of inducing strong immune protection against the challenge with Friend virus complex in H-2a/a mice. Immunologic studies demonstrated that immunized mice developed a virus-specific T cell proliferative response and showed IgM to IgG Ig class switching of virus-neutralizing antibodies. These results indicated that genetically controlled immune nonresponsiveness to F-MuLV envelope Ag in H-2a/a mice could be overcome using denatured viral envelope protein together with a strong adjuvant.
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PMID:Induction of protective immunity to Friend murine leukemia virus in genetic nonresponders to virus envelope protein. 203 65

Graft rejection, mixed chimerism, graft-versus-host disease (GVHD), leukemia relapse, and tolerance are interrelated manifestations of immunologic reactivity between donor and host cells that significantly affect survival after allogeneic bone marrow transplantation (BMT). In this report, a mouse model of BMT, in which the donor and host were compatible at the major histocompatibility complex (MHC), was used (1) to examine the interrelationship of pretransplant conditioning and T-cell content of donor BM with regard to lymphoid chimerism and GVHD and (2) to determine how these factors affected graft-versus-leukemia (GVL) reactivity and donor-host-tolerance. AKR (H-2k) host mice were administered optimal or suboptimal total body irradiation (TBI) as pretransplant conditioning followed by administration of BM cells from B10.BR (H-2k) donor mice with or without added spleen cells as a source of T lymphocytes. Transplanted mice were injected with a supralethal dose of AKR leukemia cells 20 and 45 days post-BMT to assess GVL reactivity in vivo. The pretransplant conditioning of the host and T-cell content of the donor marrow affected the extent of donor T-cell chimerism and the severity of GVH disease. GVL reactivity was dependent on transplantation of mature donor T cells and occurred only in complete chimeras. Transplantation of T-cell-deficient BM resulted in the persistence of host T cells, ie, incomplete donor T-cell chimerism, even when lethal TBI was used. Mixed chimerism was associated with a lack of GVL reactivity, despite the fact that similar numbers of donor T cells were present in the spleens of mixed and complete chimeras. In this model, moderate numbers of donor T cells facilitated complete donor T-cell engraftment, caused only mild GVHD, and provided a significant GVL effect without preventing the subsequent development of tolerance after conditioning with suboptimal TBI. In contrast, severe, often lethal, GVHD developed when the dose of TBI was increased, whereas tolerance and no GVH/GVL reactivity developed when the T-cell content of the marrow was decreased.
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PMID:Impact of pretransplant conditioning and donor T cells on chimerism, graft-versus-host disease, graft-versus-leukemia reactivity, and tolerance after bone marrow transplantation. 203 33

Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells.
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PMID:Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation. 210 13

APC activity of spleen cells from C57BL/10 (B10) mice infected with LP-BM5 murine leukemia virus (MuLV), which is known as a murine acquired immunodeficiency syndrome (MAIDS) virus, was investigated. The ability of splenic APC from LP-BM5 MuLV-inoculated B10 mice to induce soluble Ag-specific proliferation of cloned Th cells was decreased progressively during the infection. The APC defect was found to be due neither to the decreased expression of Ia Ag nor to the insufficient production of IL-1. It was demonstrated that cloned Th stimulated with virus-infected splenic APC displayed the increased [Ca2+]i with severely decreased inositol phospholipid metabolism, which probably led to the defect of Th proliferative responses. These results suggested that the failure of Th to respond to soluble Ag in MAIDS is at least in part due to a selective defect in signal transduction caused by abnormal APC.
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PMID:A selective signaling defect in helper T cells induced by antigen-presenting cells from mice with murine acquired immunodeficiency syndrome. 215 66

Anti-H-2.33 [(B10.D2 X A)F1 anti-B10.A(5R)], which predominantly contains antibodies recognizing H-2Kb and IAb molecules, was found to be cytotoxic against DMLM 1678, a B-cell leukemia of SJL/J (H-2s) origin. The antiserum precipitated a typical class I (H-2-like) molecule from labeled tumor cell preparations as judged by molecular mass, papain susceptibility and association with beta 2-microglobulin. Sequential immunoprecipitation studies revealed that it was distinct from either H-2Ks or H-2Ds, the 2 molecules expressing the private antigens of the H-2s haplotype. Absorption analysis using congenic mice mapped the gene controlling the expression of the novel molecule telomeric to the S-region within the major histocompatibility complex.
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PMID:A novel H-2s class I molecule expressed on a B-cell leukemia from SJL/J mice. 241 49

During attempts to make antibodies cross-reactive with human lymphocytes, we established a monoclonal antibody (VJ-41) from the alloimmunization of mice, that is, B10. A (3R) anti-B10. A (5R). VJ-41 reacted with all cases of freshly isolated adult T-cell leukemia cells (36 cases) but not with cells from other hematological disorders (more than 50 cases). Human T-cell leukemia virus type I healthy carriers also seemed to possess these VJ-41 antigen positive cells. However, in vitro established adult T-cell leukemia cell lines did not show the reactivity with VJ-41. Normal lymphocytes from humans or mice apparently did not carry this antigen, but mitogen activated lymphocytes or some in vitro maintained malignant cell lines of both human and mouse origins showed positive reaction. Having established solid phase radioimmunoassay to detect the VJ-41 antigen in plasma, it was found that healthy human T-cell leukemia virus type I carriers, but not the majority of adult T-cell leukemia patients, predominantly possessed this antigen. Even though immunochemical characterizations of cellular materials were unsuccessful, a certain neutral glycolipid was detected from healthy human T-cell leukemia virus type I carrier plasma by using thin-layer chromatography and immunostaining with the VJ-41 antibody.
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PMID:[Novel neutral glycolipid associated with adult T-cell leukemia and its pathological biochemistry]. 251 5

A monoclonal anti-I-Jk antibody JK10-23 was capable of precipitating the putative I-Jk molecule from NP-40 lysates of 125I-surface labelled mouse T cell clones with either helper or suppressor functions. The I-J molecule detected by specific immunoprecipitation and subsequent one- or two-dimensional gel analysis was a Mr 84-90 K dimer composed of 42-46 K glycopeptide subunits having isoelectric point pH 5.3 to 6.4. A monomeric form of I-J also existed in some of the T cell clones. The I-J subunit was a glycosylated polypeptide with a 41 K backbone having at least two glycosylation sites. I-J was distinguishable from other known dimeric T cell surface molecules with comparable molecular size, that is, T cell receptor alpha beta heterodimer, A1 and YE molecules expressed on a T cell leukemia EL4, and mouse CD28. The I-Jk molecule was precipitable from T cell clones with I-Ak and I-Ek restriction specificities including a clone derived from an H-2b----H-2bxkF1 radiation bone marrow chimera. None of the H-2b-restricted T cell clones from H-2b and its F1 showed the I-Jk immunoreactivity. T cell clones having either I-Ab or I-Ek restriction specificities derived from intra-H-2 recombinant mouse B10.A(5R) were positive for the I-Jk, while an I-Ab-restricted T cell clone from B10.A(3R) was negative in the I-Jk immunoprecipitation. The results indicate that I-J is a novel dimeric surface molecule, most likely to be a homodimer, expressed on T cells according to the major histocompatibility complex.
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PMID:Biochemical identification of I-J as a novel dimeric surface molecule on mouse helper and suppressor T cell clones. 253 59

Previous studies have demonstrated that T cell-depleted (TCD) syngeneic marrow protects against graft-versus-host disease (GVHD) when given along with an allogeneic lymphocyte plus bone marrow (BM) inoculum to lethally irradiated mice. In spite of this anti-GVHD effect, TCD syngeneic marrow is ultimately eliminated by non-TCD allogeneic marrow, permitting complete allogeneic reconstitution. These observations suggested that allogeneic BM might also eliminate host-type leukemic cells in a model in which TCD syngeneic marrow is co-administered to provide protection from GVHD. In the present studies, we describe the establishment of a new model using the EL4 leukemia/lymphoma. Lethally irradiated B10 (H-2b) mice were given a lethal dose of EL4 cells (H-2b) along with syngeneic marrow or a mixture of TCD syngeneic plus non-TCD allogeneic (B10.D2, H-2d) marrow. Non-TCD allogeneic marrow, in contrast to TCD or unmanipulated syngeneic marrow, delayed or prevented mortality from the otherwise lethal EL4 inoculum, without producing clinically apparent GVHD. The anti-leukemic effect of allogeneic marrow alone was not attenuated by the co-administration of TCD syngeneic marrow, and such animals repopulated as completely allogeneic chimeras. Similar anti-leukemic effects of mixed marrow inocula in a haploidentical strain combination, and an anti-leukemic effect against established tumor were also demonstrated. This model may have the potential to increase the safety of clinical bone marrow transplantation across greater HLA disparities, while permitting utilization of the anti-leukemic and alloengraftment-promoting effects of T cells in allogeneic marrow inocula.
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PMID:Graft-versus-leukemia effect using mixed allogeneic bone marrow transplantation. 279 Mar 25

We studied the relative importance of class I and class II major histocompatibility complex (MHC) immunoregulation in the control of T- and B-cell lymphomas induced by murine leukemia virus. Previously, we have described a mink cell focus-inducing (MCF) murine leukemia virus, MCF 1233, which induces not only lymphoblastic T-cell lymphomas but also follicle center cell or lymphoblastic B-cell lymphomas. We now report that the outcome of neonatal infection with MCF 1233 in H-2-congenic C57BL/10 and C57BL/6 mice is decisively influenced by the H-2 I-A locus. A total of 64% of H-2 I-Ak, d mice [B10.BR, B10.D2, B10.A(2R), B10.A(4R), and B10.MBR] developed T-cell lymphomas after MCF 1233 infection (mean latency, 37 weeks). In contrast, H-2 I-Ab [B10, B10.A(5R), B6], H-2 I-Ab/k [(B10.A x B10)F1 and (B10 x B10.A)F1], and H-2 I-Abm12 (bm12) mice were resistant against T-cell lymphomagenesis, but 65% of these H-2 I-Ab, b/k, bm12 animals developed B-cell lymphomas (mean latency, 71 weeks). Animals of T-cell lymphoma-susceptible strains that escaped from T-cell lymphomagenesis developed B-cell lymphomas with similar frequency as animals of T-cell lymphoma-resistant strains, but with a shorter latency. H-2 class II-determined regulation of antiviral immunity was reflected in the presence of high titers of antiviral envelope antibodies in T-cell lymphoma-resistant B-cell lymphoma-susceptible H-2 I-Ab, b/k, bm12 mice, whereas in T-cell lymphoma-susceptible H-2 I-Ak,d mice no antiviral antibodies were found. At week 4 after neonatal MCF 1233 infection, a high percentage of thymocytes were virally infected in both T-cell lymphoma-susceptible and -resistant mice. However, T-cell lymphoma-resistant animals cleared the thymic infection between weeks 4 and 10 of age, coinciding with a sharp rise in serum levels of antiviral antibodies. We conclude that the pleiotropic effects of MCF 1233 infection in H-2-congenic mice result from MHC class II I-A-determined T-cell response differences.
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PMID:Major histocompatibility complex class II-regulated immunity to murine leukemia virus protects against early T- but not late B-cell lymphomas. 284 68


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