Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific antitumor effects of lymphokine activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of IL-2 were studied. Furthermore, effects of preoperative endoscopic intratumoral injection combined IL-2 and Lentinan or OK-432 were clinically studied against gastric cancer. The results were as follows: After intratumoral consecutive injection of recombinant human IL-2 (rhIL-2), the splenocytes of these mice were cultured with rhIL-2 and the effector cells were obtained. 1) Adoptive transfer of the effector cells specifically diminished the size of the host tumor and prolonged the life span of the mice. 2) The analysis of the surface antigens indicated the Thy1.2, Thy1.2+ L3T4+ cells increased in the effector cells as the specific cytotoxicity of them were augmented. 3) Preoperative endoscopic intratumoral injection combined IL-2 and Lentinan or OK-432 induced immunocytes including antigen-presenting cells in the site of the gastric cancer, and increased the IL-2R and the LAK activity of PBL. This method was considered as effective as an adjuvant treatment of gastric cancer surgery as a in vivo sensitization.
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PMID:[Intratumoral injection of biological response modifier (BRM)]. 194 92

The development of methods of avoiding graft-versus-host disease (GVHD) while retaining the alloengraftment-promoting and anti-leukemic effects of allogeneic T cells is a major goal of research in bone marrow transplantation (BMT). We have recently obtained evidence suggesting that natural suppressor (NS) cells derived from T cell-depleted (TCD) syngeneic marrow can protect against GVHD while permitting alloengraftment. We have now attempted to enrich and then propagate NS cells in vitro, with the goal of obtaining an enhanced anti-GVHD effect by adoptive transfer in vivo. Two long-term cell lines were generated culturing BMC depleted of Mac1-positive cells and of Mac1-positive plus Thy1-positive cells in high concentrations of IL-2. Both cell lines showed anti-GVHD effects when administered along with a GVHD-producing inoculum, while permitting complete allogeneic reconstitution. A clone derived from Mac1-depleted BMC protected completely against a more chronic pattern of GVHD. These cell lines demonstrated suppressive activity in vitro, cytolytic activity against a broad range of natural killer (NK)-sensitive and NK-resistant targets, and a novel cell surface phenotype, with characteristics of both alpha beta-TcR-bearing T cells and of NK cells. In some respects, these cells resemble LAK cells and differ from fresh NS cells, and from the cloned NS cells derived from spleens of total lymphoid irradiation (TLI)-treated mice and neonatal mice. To our knowledge, this is the first detailed phenotypic analysis of cell lines with in vivo anti-GVHD activity. If applicability can be demonstrated in large animal models, the ability to use bone marrow as a source of such protective cell lines might also have potential utility in clinical BMT.
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PMID:In vitro and in vivo analysis of bone marrow-derived CD3+, CD4-, CD8-, NK1.1+ cell lines. 214 39

We have previously demonstrated that incubation of murine cells in vitro in interleukin 2 (IL-2) induced antibody-dependent cellular cytotoxicity (ADCC) and that these cells were derived from the NK/LAK, FcR+ cell population. In the present study we show that in vivo administration of IL-2 to mice induces cells which exhibit ADCC activity in the peritoneal cavity, liver, lungs, and to a lesser degree in the bone marrow, spleen, mesenteric lymph nodes, and thymus. A gradual increase in ADCC activity and the number of Fc-receptor-positive cells was seen 1 to 3 days after starting IL-2 treatment. The cells mediating ADCC are closely related to LAK cells since they expressed Thy1.2 antigens and are derived from asialo GM1-positive, Lyt2/L3T4-negative, radiosensitive cells. These results demonstrate that IL-2 can systemically induce cells with ADCC activity and that this ability may be useful in the establishment of therapeutic models against disseminated cancer when combined with specific antitumor monoclonal antibodies.
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PMID:Systemic induction of cells mediating antibody-dependent cellular cytotoxicity following administration of interleukin 2. 257 25

The cytotoxicity of spleen lymphocytes of C57BL/6 mice is augmented both by incubation of spleen lymphocytes with human recombinant interleukin-2 (rIL-2) in vitro (LAK cell) and by systemic administration of high doses of rIL-2 into C57BL/6 mice for more than 3 consecutive days. In this study, the precursors and effectors of LAK cells and the cytotoxic cells induced by systemic administration of rIL-2 were characterized by using anti-asialoGM1 and anti-Thy1.2 antibody. The in vitro induced LAK cells were demonstrated to be derived partly from asialoGM1 negative cells and the cytotoxicities of LAK cells induced in vitro with rIL-2 were partially resistant to lysis by anti-asialoGM1 antibody plus complement in comparison with NK cells. Contrary to this, the cytotoxicities of spleen lymphocytes of C57BL/6 mice pretreated with anti-asialoGM1 antibody were not augmented by in vivo injection of rIL-2. In addition, the cytotoxic activities of spleen lymphocytes, augmented by systemic administration of rIL-2, were completely suppressed by anti-asialoGM1 antibody and complement in vitro. These findings indicate that the cytotoxic lymphocytes induced in vivo by systemic administration of rIL-2 are different from in vitro induced LAK cells and have the same surface phenotype as NK cells.
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PMID:The difference in surface phenotypes between cytotoxic lymphocytes induced in vivo by systemic administration of human recombinant interleukin-2 and lymphokine activated killer cells induced in vitro. 326 91

Guanine ribonucleosides that have been substituted at the C8 position with bromine or thiol groups have been shown previously to activate NK cells and to act as sparing agents for IL-2 in the generation of LAK cells. Herein, we examined a disubstituted guanosine, 7-allyl-8-oxoguanosine (loxoribine), for the ability to activate NK cells and to interact with IL-2 in the generation of LAK cells. Loxoribine enhanced the NK activity of murine spleen cells with optimal activity occurring after 10 h of culture at concentrations ranging from 50 to 150 microM. The response was, however, short lived, approaching baseline levels by 24 h of culture. In contrast, if spleen cells were cultured with a suboptimal concentration of IL-2 (10 U/ml) in combination with loxoribine, a prolonged and enhanced cytolytic activity was seen. The enhancement was greatest if the loxoribine and IL-2 were both added to the cultures at the beginning of the incubation period. Analysis of the expression of the alpha-chain of the IL-2 receptor after loxoribine stimulation indicated that gene transcription was enhanced within 4 h, and cell surface expression was observed on NK1.1+ Thy1+ and NK1.1+ Thy1- cell populations within 24 h of loxoribine treatment. The priming of LAK cell precursors by loxoribine did not appear to be mediated by IFN-alpha/beta, because anti-IFN antibodies did not block either the activation of cytolytic cells by IL-2 or the expression of IL-2 receptors after culture with loxoribine. These data suggest that one mechanism by which cytolytic precursor cells are primed by loxoribine to respond to IL-2 faster and with enhanced cytolytic activity may be through the expression of high affinity IL-2 receptors due to the up-regulation of the alpha-chain.
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PMID:Loxoribine (7-allyl-8-oxoguanosine) activates natural killer cells and primes cytolytic precursor cells for activation by IL-2. 837 66

IL-5 synergies with IL-2 to produce increased LAK activity, although IL-5 alone induced little cytotoxic activity. The most dramatic synergy occurred with a suboptimal IL-2 concentration. The kinetics of LAK activity induced by IL-2 plus IL-5 were similar to those induced by IL-2. IL-5 exerted its effects during the late stage of IL-2 induced LAK generation. In the precursor phase, depletion of asialo-GM1+ cells preceding culture eliminated IL-2 plus IL-5 induced LAK activity. In the effector phase, IL-2 plus IL-5 induced LAK activity was eliminated by depletion of Thy1.2+ cells following culture.
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PMID:Synergy of interleukin-5 with interleukin-2 in the generation of lymphokine-activated killer-cells. 2158 27