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)

The effect of salazosulfapyridine (SASP) on the antibody response of murine spleen cells in vitro was studied. SASP inhibited the response to sheep red blood cells (SRBC), a T-cell-dependent (TD) antigen, dose-dependently and was most effective at a dose of 2 x 10(-4) M without cell toxicity. No remarkable inhibition was seen with the main metabolites of SASP, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP). SASP failed to inhibit antibody production to T-cell-independent antigens such as dinitrophenyl-Ficoll or trinitrophenyl (TNP)-lipopolysaccharides, although the response to TNP-keyhole limpet hemocyanin, another TD antigen like SRBC, was inhibited. Further, this drug did not show any depression of the anti-SRBC plaque-forming cell (PFC) response in spleen cells treated with anti-Thy1.2 antibody plus complement. The inhibition of anti-SRBC PFC response by SASP was accompanied by a reduction of interleukin 2 (IL-2) secretion. Our results suggest that SASP may act on T cell populations and may inhibit the T-cell-dependent antibody response partly through a depression of IL-2 production. The active compound appears to be SASP itself, rather than its metabolites.
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PMID:The effect of salazosulfapyridine on the in vitro antibody production in murine spleen cells. 196 49

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

It is generally accepted that T lymphocyte-mediated autoimmunity contributes to the pathogenesis of Type 1 diabetes in humans and animals. Using spleen cells from nonobese diabetic (NOD) mice, a model of human Type 1 diabetes, we have analyzed the subset of T lymphocytes by flow cytometry and investigated concanavalin A (Con A)-induced interleukin 2 (IL-2) production and cell proliferation. NOD mice showed a higher percentage of Thy1.2+, L3T4+, and Lyt2+ T lymphocytes than did control ICR mice through the whole age examined. Spleen cells from a large majority of NOD mice were found to generate very low IL-2 production and cell proliferation in response to Con A. However, a few mice preserved their responsiveness to Con A. The following reasons may indicate that macrophage-mediated suppression participates in the deficient function of NOD spleen cells. (a) Macrophage depletion from NOD spleen cells retrieved Con A-induced IL-2 production. (b) Thioglycollate-induced peritoneal exudate cells containing many activated macrophages could completely suppress cell proliferation. (c) Prostaglandin synthetase inhibitor indomethacin reversed the suppression of IL-2 production by macrophages. (d) Conversely, exogenous prostaglandins could show the partial suppression of IL-2 production. These results suggest that activated macrophages suppress the response of NOD spleen cells to Con A mostly through prostaglandins. This impairment may contribute to the pathogenesis of Type 1 diabetes in NOD mice.
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PMID:[Cellular immune dysfunction in the NOD mouse: suppression of concanavalin A-induced responses in spleen cells by activated macrophages]. 258 13

The effects of the alkaline earth divalent cation Barium (Ba2+) were studied in in-vitro murine polyclonal T cell activation induced with a panel of T cell mitogens consisting of the plant mitogens concanavalin A (ConA), jacalin and phytohaemagglutinin (PHA), a mitogenic anti-Thy1 monoclonal antibody (MoAb), and an anti-murine CD3 MoAb combined with phorbol ester. All modes of T cell activation, except PHA-induced mitogenesis, were blocked in a reversible and dose-related manner by Ba2+. Blockade was evident only if Ba2+ was added within the first 6 h of stimulation, was totally reversed in a competitive fashion by addition of Ca2+ to the medium, and selectively affected interleukin 2 (IL-2) production, without interfering with expression of IL-2 receptor light chains, nor with late IL-2-dependent activated T cell growth. On the other hand, PHA-induced responses stimulated by optimal mitogen doses were resistant to the effects of Ba2+. Ba2+-resistance of PHA responses was due to IL-2-dependent activation and growth of a Ba2+-resistant T cell subset since: (i) limiting dilution analysis demonstrated that this PHA response had a much lower precursor cell frequency than control PHA responses; (ii) proliferation was blocked by anti-IL2 agents, such as cyclosporin A and anti-IL-2 receptor light chain MoAbs, which were much less effective in blocking control PHA responses. Thus, pharmacological use of Ba2+ reveals the existence of a pathway of T cell activation, induced by PHA, with differential interleukin requirements.
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PMID:Functional heterogeneity in the process of T lymphocyte activation; barium blocks several modes of T cell activation, but spares a functionally unique subset of PHA-activable T cells. 278 51

The present report describes evidence to show that interleukin 2 (IL-2), in addition to its well known action as a second signal in mitogenic action on mature T cells, functions as a regulator of both proliferation and maturation of immature T lymphocytes. The present experiments extend previous observations indicating that immature thymocytes (Thy1+, L3T4-, Ly2-) are a target of IL-2 action. IL-2 and thymosin fraction V but not interleukin 1 (IL-1) induce differentiation of prothymocytes (Thy1-, L3T4-, Ly2-) obtained from spleens of nude mice as measured by the acquisition of the Thy 1 marker. IL-2, but not thymosin fraction V and IL-1, modulates the proliferation of this cell population. The data indicate that IL-2 may exert a significant regulatory function in T cell ontogeny.
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PMID:Effects of T cell growth factor/interleukin II on prothymocytes. 287 24

The effect of in vivo administration of recombinant interleukin 2 (rIL2) on the growth of a primary female BALB/c sarcoma induced by Moloney murine sarcoma virus (M-MSV) was studied. Although low-dose administration of (6,000 JU/mouse x 14 days) rIL2 had no effect on the growth of the tumors, high-dose (15,000-80,000 JU/mouse x 14 days) intraperitoneal inoculation of rIL2 induced tumor regression, dose-dependently. Tumors in mice which received 80,000 JU/mouse/day of rIL2 regressed completely 2 weeks after the initiation of treatment. The survival rates of the treated groups were significantly higher than those of the control group. A time course experiment disclosed that the effect of rIL2 was restricted only to the group in which rIL2 treatment started 8 days after the inoculation of M-MSV. The cytotoxic activity of regional lymph node lymphocytes from rIL2-treated mice was demonstrated against primary culture of M-MSV-induced sarcoma but not against syngeneic tumor induced by methylcholanthrene (Meth A). The effect of rIL2 was partially blocked by the administration of anti-IL2 receptor antibody. Immunohistochemical examination revealed that infiltration of Thy1.2+Lyt1+2- (helper/inducer subset) lymphocytes into the tumor tissue was prominent in mice which received high-dose rIL2. The results indicated that IL2 induced regression of M-MSV-induced sarcoma mainly through activation of IL2-receptor-positive helper T cells in the tumor tissues and of killer cells in the draining lymph nodes.
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PMID:Effect of recombinant human interleukin 2 on the growth of a BALB/c sarcoma induced by Moloney murine sarcoma virus. 314 31

The lymphocyte activating properties of a membrane proteoglycan (MPG) extracted from a mutant non-encapsulated strain of Klebsiella pneumoniae (Kp) (biotype a I-145) were investigated. Kp MPG induced a strong proliferative response of BALB/c spleen cells and Peyer's patches cells. Thymidine incorporation was dose-related (from 1 to 100 micrograms Kp MPG/ml) and reached a maximum at day 3. It was not reduced by removal of most adherent cells, nor by depletion of Thy1-2 positive cells, but it was abrogated by removal of surface immunoglobulin bearing cells. Spleen cells from nude mice and those from C3H/Hej mice were strongly stimulated by Kp MPG. Conversely Kp MPG did not induce interleukin 2 production and did not trigger the proliferation of thymocytes but stimulated interleukin 1 production by adherent spleen cells. Finally, unfractionated or B-enriched spleen cells cultured with Kp MPG synthesized IgM and, to a lesser extent, IgG and IgA. It is concluded that Kp MPG is a T-independent polyclonal B cell activator and an inducer of interleukin 1 production.
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PMID:Polyclonal activation of murine B cells by a membrane proteoglycan of Klebsiella pneumoniae. 331

A new model for the generation of specific antitumor cytotoxic T lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate secondary effector CTL (CTL-2) without tumor stimulator cells in vitro (in monoculture). C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes after 1-fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1-fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2, CD8+, CD4- phenotype. Presence in vitro of exogenous recombinant interleukin 2 (rIL-2) was needed for the generation of CTL-2 against Mech-11 sarcoma but not against EL4 lymphoma. The spleen cells from B10 mice with progressively growing Mech-11 tumor specifically suppressed the maturation of CTL-2 against Mech-11 in monoculture. Since suppression took place in the presence of exogenous rIL2 in monoculture, it was suggested that suppression was not resulted by negative influence of the suppressor cells upon endogenic IL-2 production. The treatment of the suppressor cells with monoclonal antibody (Mab) against Thy1.2 as well as against CD4 or CD8 markers plus complement (C') considerably decreased Ts activity. Obviously, two distinct subsets of T-lymphocytes were required for suppression.
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PMID:Generation of specific antitumor cytotoxic T-lymphocytes in monoculture can be inhibited by T-suppressors from tumor-bearing mice. 781 61

Chronic graft-versus-host disease (GVHD) can be induced in B6D2F1 mice by injection of parental DBA/2 lymphoid cells. Stimulation of donor T cells by host MHC antigens leads to the stimulation of host B cells. Little is known of the lymphokines produced during such a reaction. This study was designed to directly measure the levels of mRNA for interferon-gamma (IFN-gamma), interleukin 2 (IL-2), IL-4, IL-5, and IL-10, as well as several other genes, using semiquantitative polymerase chain reaction (PCR). Semiquantitative PCR was reproducible and signals generated were dependent on the amount of specific RNA or cDNA in each reaction. Early during the progression of GVHD (2 days after the first injection of parental cells) there was little increase in IL-10 mRNA, a slight increase in IL-4 mRNA, and a dramatic increase in IL-2 mRNA. In addition, IL-2 bioactivity was demonstrated in supernatants from GVH splenocytes cultured in vitro for 24 h. Later in the response (1 week after the second and final injection of parental cells) IL-4 mRNA levels were elevated as they were earlier while IL-10 mRNA levels were dramatically increased. IL-2 mRNA levels were no different in mice undergoing GVHD than in normal mice at this time. IFN-gamma mRNA was detectable both early and late, although at similar levels in normal mice and mice undergoing GVHD. At both times examined, IL-4 was below the limits of detection by bioassay and IFN-gamma, IL-4, IL-5 and IL-10 were below the limits of detection by ELISA. Further studies showed that a majority of the IL-4 and IL-10 mRNA found elevated in GVH mice were produced by Thy1.2+ T cells, with small amounts from B220+ B cells. In addition, the detectable IFN-gamma mRNA found in GVH mice at this later time also was produced by Thy1.2+ T cells, with small amounts from B220+ B cells.
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PMID:Cytokine gene expression in mice undergoing chronic graft-versus-host disease. 848 82