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

T-cell-replacing factor (TRF) is a T-cell-derived factor required for terminal differentiation of activated B cells to immunoglobulin-secreting cells. Previous studies have shown that a murine T-cell hybrid (B151K12) produces factor(s) that (i) induce immunoglobulin secretion by the B-cell leukemia line BCL1 and secondary anti-2,4-dinitrophenyl IgG synthesis in vitro by dinitrophenyl-primed B cells (TRF activity) and (ii) cause proliferation of the BCL1 cells [B-cell growth factor II (BCGF-II) activity]. Both activities appear to be associated with the same molecule. Here we report the production of a monoclonal antibody to murine TRF. The monoclonal antibody, designated TB13, strongly inhibited both TRF and BCGF-II activities and absorbed TRF- as well as BCGF-II-active molecules produced by B151K12 and by Xenopus oocytes that had been injected with mRNA transcribed from plasmid pSP6K-mTRF23. Inhibition was linearly dependent on the concentration of both TB13 and TRF. Monoclonal antibody TB13 did not inhibit the activities of B-cell stimulatory factor 1, interleukin 1, interleukin 2, or interleukin 3. TRF activity in dissolved samples of immunoprecipitates obtained with TB13 was recovered after NaDodSO4/PAGE, in the fractions corresponding to a protein band at Mr 46,000. Our results indicate that monoclonal antibody TB13 recognizes a molecule that has both TRF and BCGF-II activities.
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PMID:Production of a monoclonal antibody useful in the molecular characterization of murine T-cell-replacing factor/B-cell growth factor II. 244 25

The purpose of this study was to examine the role of IL-1 on the activation of CD8+/CD4- class I-restricted helper cell-independent cytolytic T cell (HITc) clones known to produce IL-2 and proliferate in vitro after Ag stimulation with a Friend retrovirus-induced leukemia (FBL). The functional role of IL-1 in Ag-specific proliferation and IL-2 secretion was assessed by stimulating the T cell clones with FBL either in the presence or absence of macrophages (M phi), rIL-1, or rIL-2. Resting cloned HITc cells, purified from residual accessory cells, failed to proliferate in response to FBL alone, but proliferated in response to FBL plus M phi, rIL-1 or rIL-2. Stimulation with FBL alone in the absence of M phi or IL-1 was sufficient for induction of IL-2R expression, and rendered cells responsive to IL-2, but M phi or IL-1 were also required to induce production of IL-2. The activity of IL-1 was further examined by measuring the binding of [125I]rIL-1 alpha, which demonstrated that resting cloned HITc cells expressed IL-1R that increased in number after activation with Ag. This expression of IL-1R and requirement for IL-1 by CD8+ HITc was surprising because previous studies examining T cell populations after mitogen stimulation have not detected IL-1R on the CD8+ population. Therefore, the role of IL-1 in the activation of CD8+ CTL that do not secrete IL-2 after activation was assessed. By contrast to HITc, CD8+ CTL required exogenous IL-2 to proliferate in vitro and did not express IL-1R. These data demonstrate that the subset of CD8+ T cells responsible for IL-2 production express IL-1R and that triggering this receptor with IL-1 after Ag stimulation results in the production of IL-2 and subsequent proliferation.
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PMID:Helper-independent CD8+ cytotoxic T lymphocytes express IL-1 receptors and require IL-1 for secretion of IL-2. 246 90

An adoptive therapy model has been utilized to examine the requirements for T cells to promote eradication of a disseminated, retrovirus-induced, syngeneic leukemia. Complete tumor elimination required that the transferred T cells proliferate in the host and mediate an anti-tumor effect for more than 30 days. Non-cytolytic L3T4+ T helper (Th) cells were capable of eliminating disseminated tumor without the participation of Lyt-2+ cytotoxic T cells (Tc). Purified or cloned Lyt-2+ T cells were also effective in therapy, but required the concurrent administration of either L3T4+ Th or interleukin 2 (IL-2) for optimal efficacy. L3T4+ Th appear to function via secretion of lymphokines that activate macrophages to a cytotoxic state. Lyt-2+ Tc, in addition to direct cytotoxicity, may mediate tumor eradication in part by secretion of lymphokines that activate in vivo tumoricidal macrophages. These studies suggested that the reported efficacy of individual T cell subsets in therapy of particular tumors might not reflect resistance or susceptibility to a cytotoxic effector mechanism, but rather the efficiency with which a T cell subset is activated by the tumor and/or recognizes the tumor antigen. Methods were developed to independently assess the activation and proliferation requirements of each subset. L3T4+ Th required that macrophages degrade tumor antigens in lysosomes and present the antigens in the context of class II molecules, and produced IL-2 and IL-4 as endogenous growth factors. By contrast, Lyt-2+ T cells recognized the tumor directly, required macrophages only to produce IL-1 for activation, and produced IL-2 but not IL-4 as an endogenous growth factor. The ability of T cell subsets to recognize the distinct retroviral tumor antigens expressed on FBL leukemia was assessed using cell lines or recombinant vaccinia viruses transfected with selected retroviral genes. Highly selective antigen recognition was detected, with Lyt-2+ Tc cells recognizing products of gag but not envelope genes, and L3T4+ Th recognizing envelope but not gag products. The results suggest that even complex unique tumor antigens may elicit only limited host T cell responses.
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PMID:Requirements for T cell recognition and elimination of retrovirally-transformed cells. 247 34

Production of interleukin 1 (IL-1) by leukemic cells was studied in 13 cases of acute myeloid leukemia. Intracytoplasmic immunofluorescence studies showed that the cells invariably contained the cytokine. Endogenous labeling studies demonstrated that acute myeloid leukemia cells produced either only the 33-kDa propeptide or both the propeptide and the 17-kDa mature form of IL-1 beta. The 33-kDa propeptide IL-1 alpha was always produced but was less frequently released. Involvement of IL-1 in leukemic cell growth was investigated using two antibodies specific for IL-1 subtypes, which inhibited spontaneous cell proliferation in the six cases studied. After acid treatment of the cells, a surface receptor for IL-1 could be demonstrated, which mediated 125I-labeled IL-1-specific uptake by leukemic cells. Furthermore, recombinant IL-1 alpha or IL-1 beta induced significant cell proliferation in 10 of 12 cases. The above findings were uncorrelated with the cytologic type (French-American-British classification) of leukemia. Our studies suggest that IL-1 may act as an autocrine growth factor in most cases of acute myeloid leukemia.
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PMID:Interleukin 1 as an autocrine growth factor for acute myeloid leukemia cells. 252 58

Two types of activation Ag, low affinity FcR for IgE (Fc epsilon R2)/CD23 and IL-2R (Tac/p55), were expressed and differently regulated on human eosinophilic leukemia cell lines (EoL-1 and EoL-3). Because the binding of IgE on EoL-3 cells was completely inhibited by H107 (anti-Fc epsilon R2/CD23 mAb) but not by irrelevant mAb, essentially all the low affinity Fc epsilon R2 on EoL-3 seemed to be the Fc epsilon R2/CD23 molecules. Both IL-4 and IFN-gamma enhanced the surface expression of Fc epsilon R2, whereas IL-1, IL-2, and IL-5 showed no effects, as determined by surface staining with anti-Fc epsilon R2 antibody (H107). In contrast to Fc epsilon R2 up-regulation, IL-4 and IFN-gamma showed a differential effect on the regulation of IL-2R (Tac/p55). Whereas IFN-gamma up-regulated the receptor expression of IL-2R/Tac, IL-4 did not. The result suggests that these lymphokines are involved in the different aspects of the activation pathway of the eosinophils. The possible role of Fc epsilon R2 and IL-2R on the function of eosinophils in allergic reaction is discussed.
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PMID:Differential regulation of the low affinity Fc receptor for IgE (Fc epsilon R2/CD23) and the IL-2 receptor (Tac/p55) on eosinophilic leukemia cell line (EoL-1 and EoL-3). 252 45

The development of a cell culture system for the in vitro cloning and clonal differentiation of normal hematopoietic cells made it possible to identify the proteins that regulate growth and differentiation of different hematopoietic cell lineages and the change in normal controls that produce leukemia. A model system with myeloid cells has identified different myeloid cell colony-inducing proteins, which we called MGI-1 (= CSF, including IL-3). There is another protein that we first described in 1976 and called MGI-2 in 1980 that induces differentiation of myeloid cells to macrophages or granulocytes without inducing the clonal growth of myeloid cells. The four CSF proteins and IL-1 induce the production of MGI-2 in myeloid cells and MGI-2 induces the production of GM-CSF. This shows the participation of MGI-2 in the network of interactions with different myeloid regulatory proteins. Using a monoclonal antibody to MGI-2, amino acid sequencing, and recombinant protein, we have shown in collaboration with the Genetics Institute that the major form of MGI-2 (MGI-2A) is IL-6. This shows that IL-6 is a myeloid cell differentiation inducing protein. The results also suggest new clinical potentials for MGI-2/IL-6.
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PMID:The molecular regulators of macrophage and granulocyte development. Role of MGI-2/IL-6. 266 Jun 99

We have cloned a previously undescribed adhesion molecule, VCAM-1, which is induced by cytokines on human endothelial cells and binds lymphocytes. Using a novel method requiring neither monoclonal antibodies nor purified protein, VCAM-1-expressing clones were selected by adhesion to human lymphoid cell lines. VCAM-1 mRNA is present in endothelial cells at 2 hr after treatment with IL-1 or TNF-alpha and is maintained for at least 72 hr; leukocyte binding activity parallels mRNA induction. Cells transfected with VCAM-1 bind the human leukemia lines Jurkat, Ramos, Raji, HL60, and THP1, but not peripheral blood neutrophils. VCAM-1, which belongs to the immunoglobulin gene super-family, may be central to recruitment of mononuclear leukocytes into inflammatory sites in vivo.
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PMID:Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. 268 98

In a previous study, we reported that adult T-cell leukemia (ATL) cells produce interleukin 1 (IL1)-like factors that stimulate murine thymocyte proliferation, the production of interleukin 2 (IL2), and the expression of IL2 receptors (IL2R) on normal human T-cells in the presence of concanavalin A. In this communication, we studied the effect of IL1 on the growth of ATL cells in vitro. When ATL cells freshly obtained from patients were cultured with recombinant (r) human IL1 alpha, IL1 beta, or IL1-like factors produced by ATL cell lines, the growth of ATL cells was stimulated in a concentration-dependent manner. Maximum stimulation was observed at a concentration of 50-100 units/ml of IL1. The expression of IL2R on ATL cells was also enhanced by IL1, but the production of IL2 was not induced. These effects of rIL1 alpha or beta were specifically inhibited by anti-IL1 alpha or anti-IL1 beta antibody. Furthermore, the spontaneous growth of ATL cells was also inhibited by anti-IL1 alpha antibody, but not by anti-IL1 beta antibody. ATL cells exhibited enhanced expression of IL1 receptors on their surface as detected by the binding of 125I-labeled rIL1 alpha. These results suggest that IL1 alpha produced by ATL cells stimulates the growth of ATL cells by an autocrine mechanism.
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PMID:Autocrine stimulation of interleukin 1 alpha in the growth of adult human T-cell leukemia cells. 278 84

The effect of a short synthetic fragment of human interleukin-1 beta (hu IL-1 beta) on natural killer (NK) activity was examined. Peripheral-blood mononuclear cells (PBMC) from normal donors showed a significant increase in NK activity against K562 leukemia cells after preincubation for 18 h with the IL-1 peptide. A similar augmentation was not observed after culturing the cells in the presence of hu IL-1 beta. The increase in tumor cell lysis could not be ascribed to a cytolytic activity of the synthetic fragment on target cells, since the peptide caused no direct lysis of various tumor cell lines. Although the peptide enhanced NK cytotoxicity of PBMC, highly purified large granular lymphocytes were not susceptible to its stimulatory effect. The addition to the cultures of antibodies to human interleukin-2 (hu IL-2) completely blocked the peptide-induced boost of NK cytotoxicity, suggesting that IL-2 is mainly involved in the activation process. The ability of the IL-1 peptide to increase NK activity was further confirmed in vivo in the mouse. Cytotoxicity against YAC-1 lymphoma cells, which was very low in the spleen of untreated BALB/c mice, was in fact significantly increased after a single inoculation of the peptide. These data thus indicate that a short synthetic peptide fragment of hu IL-1 beta is able to increase both human and murine NK activity.
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PMID:A short synthetic peptide fragment of human interleukin-1 beta increases both human and murine natural killer activity. 278 40

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.
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PMID:Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera. 278 62


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