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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Upon infection of human T-cell leukemia virus type I (HTLV-I)-carrying human T-cell lines such as MT-4, HTLV-III, a probable etiologic agent of acquired immune deficiency syndrome (AIDS) caused fast and strong cytopathic effects leading ultimately to the death of the cells. Such effects were preceded by the rapid induction of HTLV-III antigens. Cell lines not infected with HTLV-I could, however, be subcultured after infection with HTLV-III, although they were also positive for HTLV-III antigens. To understand this cytopathogenicity of HTLV-III in HTLV-I bearing cells, macromolecular synthesis, including DNA synthesis and total protein synthesis, and also IL-2 receptor expression were investigated kinetically. In infected MT-4 cells DNA synthesis was markedly inhibited by HTLV-III after the HTLV-III antigen synthesis became evident. This inhibition occurred before cell damage was detected in terms of viable cell-growth, but after induction of HTLV-III antigen. Puromycin, at 40 micrograms/ml, caused no toxic changes in MT-4 cells over 3 days but prevented viral antigen synthesis and virus-induced cytopathic effect. Protein synthesis and IL-2 receptor expression were also inhibited at 4 and 5 days post infection. The degree of the effects and their kinetics suggest that they are the secondary effects of cytotoxicity by HTLV-III infection.
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PMID:Effect of HTLV-III on the macromolecular synthesis in HTLV-I carrying cell line, MT-4. 302

A region of homology has been found between the envelope (env) protein of the acquired immunodeficiency syndrome (AIDS) virus and a portion of interleukin 2 (IL-2) that purportedly binds to the IL-2 receptor. This homology, between two proteins associated with opposing biological functions, suggests possible mechanisms for the immunosuppressive activity of the AIDS virus. Two mechanisms are proposed in which the AIDS virus env protein interferes with IL-2 activity either directly or indirectly. A region of similarity to the purported IL-2 receptor binding site on IL-2 and AIDS virus env is present in the env proteins of other retroviruses associated with immunosuppression. A synthetic peptide vaccine for AIDS is suggested based on the IL-2 receptor binding sequence in AIDS virus env.
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PMID:Sequence homology between acquired immunodeficiency syndrome virus envelope protein and interleukin 2. 302 69

Five of 22 hemophiliacs who were seropositive for human T cell leukemia virus III (HTLV III) and manifested severe impairment of immune parameters (both in vivo and in vitro) similar to those observed in patients with clinical symptoms of acquired immune deficiency syndrome (AIDS) were chosen for this study. Profound lymphopenia was observed in four of five patients with decreased and qualitatively impaired helper/inducer (T4) cells and increased T suppressor/cytotoxic (T8) cells. Observed in all patients was impaired endogenous production of interleukin-2 (IL-2), expression of the IL-2 receptor combined with diminished responses to mitogens, mixed leukocytes reaction (MLR), and natural killer (NK) reactivity. In vitro supplement of exogenous IL-2 markedly augmented T and NK cell functions, as well as the expression of activation antigens on both T4 and T8 cell in four of five patients. Our findings suggest that a substantial proportion of this cell-mediated immunologic defect in hemophiliacs stems from their inability to produce adequate amounts of IL-2. Interleukin-2 may therefore have the potential for therapy as an immune response modifier in patients with hemophilia by providing beneficial preventive therapy for patients at risk.
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PMID:In vitro restoration by interleukin-2 (IL-2) of the impaired natural killer cell activities, IL-2 receptor expression, and T cell proliferation in hemophilia. 309 Feb 9

A region of human interleukin-2 (IL-2) which was predicted to be a contact point with its receptor was used to locate a homologous region in the envelope protein of human T-lymphotropic retrovirus (HTLV-III). This homologous six amino acid peptide from the carboxy (C)-terminus of the HTLV-III envelope protein was found to inhibit the biological activity of human IL-2 in a murine spleen cell proliferation assay. When conjugated to a carrier protein, this peptide inhibited the binding of radiolabelled IL-2 to its receptor. The biological activity of the peptide was antagonized by a six amino acid peptide fragment of the IL-2 receptor which was predicted to be the contact point on the receptor that corresponded to the binding region of IL-2. The HTLV-III peptide also inhibited the binding of radiolabelled IL-2 to polyclonal anti-IL-2 antiserum. These data support the previous assignment of contact points between IL-2 and its receptor. They also suggest two possible mechanisms of immunosuppression during acquired immunodeficiency syndrome (AIDS). One involves direct competition of the envelope protein or its fragments with IL-2 for binding to the IL-2 receptor. The other involves antibodies to the envelope protein which crossreact with and neutralize IL-2.
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PMID:The HTLV-III envelope protein contains a hexapeptide homologous to a region of interleukin-2 that binds to the interleukin-2 receptor. 309 12

A sensitive monoclonal antibody based ELISA was used to detect cell-free interleukin-2 receptor (IL-2R) in the body fluids of patients with acquired immune deficiency syndrome (AIDS), a variety of other disease conditions and a control group of apparently healthy (heterosexual and homosexual) males. Two of the 25 control donors showed low titers (1:8) of IL-2 receptor in the serum samples; the cerebrospinal fluid (CSF) specimens from these individuals proved negative. However, serum and CSF specimens from all the 9 patients with AIDS showed significantly elevated titers (range 1:128 to 1:4096) of IL-2 receptor. The presence of moderate titers (range 1:128 to 1:512) of circulating IL-2 receptor could also be detected in all of the 4 patients with acute lymphocytic leukemia. IL-2 receptor was detectable in the CSF and/or serum specimens from 3 of 3 patients with lung cancer, 3 of 4 patients with acute hepatitis B infection, and 2 of 3 patients with multiple sclerosis. IL-2 receptor could not be detected in the serum or CSF specimens originating from patients with legionellosis (3/3), asthma (3/3), or those with non-pulmonary febrile bacterial infections (4/4). It is concluded that soluble IL-2 receptor may be found in serum or CSF specimens from patients with certain (but not all) disease conditions including AIDS. The conspicuously elevated titers of cell-free IL-2R in the body fluids of patients with AIDS may contribute to the drastic impairment of the immune system regulation observed in such patients.
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PMID:Elevated titers of cell-free interleukin-2 receptor in serum and cerebrospinal fluid specimens of patients with acquired immunodeficiency syndrome. 309 29

We investigated the expression of the interleukin-2 (IL-2) receptor on phytohaemagglutin-stimulated peripheral blood lymphocytes from homosexual men with persistent generalized lymphadenopathy, the prodrome of the acquired immune deficiency syndrome. The subjects were positive for antibody against human T-cell lymphotropic virus III. Using two-colour fluorescence flow cytometry, IL-2 receptor expression was determined on both the CD4- and CD8-positive lymphocyte subpopulations. After 48 hr of stimulation, expression of the IL-2 receptor on both T-cell subsets was significantly increased in lymphadenopathy patients as compared to values in heterosexual age-matched controls; this difference was less after 72 hr of stimulation. Results from two AIDS patients were within the normal range. IL-2 production was significantly reduced in both lymphadenopathy and AIDS patients as compared to values in heterosexual controls. We conclude that a defect in IL-2 production is associated with human T-cell lymphotropic virus III infection, but that the expression of the IL-2 receptor on T cells is not greatly affected.
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PMID:Increased interleukin-2 receptor expression after mitogen stimulation on CD4- and CD8-positive lymphocytes and decreased interleukin-2 production in HTLV-III antibody-positive symptomatic individuals. 310 Apr 39

Sera from patients with acquired immune deficiency syndrome (AIDS) were analysed for effects on normal lymphocyte interleukin 2 (IL-2) production, IL-2 receptor (IL-2R) expression and levels of IL-2 dependent T cell proliferation. The presence of AIDS serum appeared to reduce significantly IL-2 production by cultures of mitogen-activated normal human peripheral blood mononuclear cells (PBMC). However, dilution analyses of the culture supernatants indicated that the primary inhibitory effect occurred at the level of the IL-2 responsive target cell. Furthermore, eight of nine AIDS sera, but none of the normal human sera (NHS) tested, suppressed the capacity of IL-2-dependent CTL-20 cells to proliferate in response to human IL-2. Fractionation of AIDS sera by gel filtration on Sephacryl S-200 revealed that inhibitory activity coeluted with the immunoglobulin fraction. Pretreatment of human IL-2R+ lymphoblasts with AIDS serum did not interfere with the binding of monoclonal antibody (anti-Tac) specific for the human IL-2R; however, significant reductions in the levels of phytohaemagglutinin-induced IL-2R expression were observed when normal human PBMC were cultured in the presence of AIDS serum. These findings indicate that the inhibitor present in many AIDS sera does not suppress lymphocyte proliferation by interfering directly with the IL-2 receptor, and suggest that inhibition occurs at a later stage of the cell cycle. One of the primary consequences of the activity of this serum inhibitory factor is a decline in the levels of lymphocytic IL-2R expression.
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PMID:Humoral-mediated suppression of interleukin 2-dependent target cell proliferation in acquired immune deficiency syndrome (AIDS): interference with normal IL-2 receptor expression. 311 47

There has been interest in the potential of synthetic compounds to modify immune responses by imitation of cytokine action. Direct administration of interleukin 2 (IL-2) in conjunction with adoptive transfer of lymphokine activated killer cells has been used in the treatment of cancer, but there are toxic effects resulting from the high doses of IL-2 required. We have developed a new synthetic compound, ammonium tri-chloro(dioxoethylene-O,O'-)tellurate (AS-101), which has immunomodulating properties and minimal toxicity. The effects of AS-101 on the activation and function of immunocompetent cells have been assessed. We have found that AS-101 induces proliferation and IL-2 production by human lymphocytes in vitro, and enhances the production of IL-2 and colony-stimulating factor by mouse spleen cells. Splenocytes of BALB/c mice injected with AS-101 increased production of IL-2 and CSF in vitro in the presence of mitogen. Mononuclear cells of normal donors acquired responsiveness to recombinant IL-2 and bound monoclonal antibody to IL-2 receptor after incubation with AS-101. Splenocytes of mice treated in vivo with AS-101 expressed high levels of IL-2 receptor. The stimulation of lymphocytes by AS-101 apparently involves an increase in intracellular free calcium. AS-101 administered systemically to mice mediated antitumour effects which could be attributable to its immunomodulatory properties. In addition, AS-101 could directly enhance the ratio of OKT4 to OKT8-positive cells in cultured mononuclear cells from AIDS (acquired immune deficiency syndrome) patients. These results indicate that AS-101 is potentially useful in the treatment of clinical conditions involving immunosuppression.
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PMID:A new immunomodulating compound (AS-101) with potential therapeutic application. 311 16

AS-101 (ammonium trichloro[dioxoethylene-O,O'-]tellurate) is a newly developed synthetic compound with immunomodulating properties and minimal toxicity. We evaluated the effects of AS-101 on various parameters of the activation and function of immunocompetent cells. AS-101 induced IL-2 receptor expression, IL-2 production and proliferation by human and mouse lymphocytes in vitro and enhanced the production colony-stimulating factor (CSF) by mouse spleen cells. In vivo treatment of Balb/c mice with AS-101 caused a significantly increased production of IL-2 and CSF in vitro in the presence of mitogen. When administered systemically to mice, AS-101 mediated antitumor effects in vivo. These results suggest that AS-101 is an active biological response modifier, which might have potential use in the treatment of conditions such as malignancy, AIDS and some types of immune deficiency.
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PMID:The biological activity and immunotherapeutic properties of AS-101, a synthetic organotellurium compound. 326 21

This review covers significant developments in the understanding of the biochemistry and clinical pharmacology of Interleukin-2 (IL-2) that were achieved from 1984 through September 1986. These include developments in the molecular biology of IL-2 and its receptors. Human IL-2 was cloned and sequenced by Taniguchi et al. in 1983. The gene for human IL-2 is located on the long arm of chromosome 4. The secondary structure of the gene is predominantly alpha helix. The mature gene product is a 133 amino acid glycoprotein with a molecular weight of 15,420 Daltons. The IL-2 receptor was revealed to be a glycoprotein of 272 amino acids. The mature receptor has a molecular weight of 55,000 Daltons. A more precise understanding of the mechanism of action IL-2, in particular its role in the induction of the IL-2 receptor, and aspects of the control of IL-2 production was also achieved. Metabolic and morphologic studies have revealed that activation of the T-cell antigen receptor renders the cells responsive to IL-2, but does not move them through the cell cycle. Rather, it appears that IL-2 stimulates G1 progression to S phase ie. blastic transformation. During this progression the cellular proto-oncogene c-myb is induced transiently to 6 to 7 times basal levels. The role of IL-2 as a growth factor for several subsets of T cells has been confirmed, and a new role as a growth factor for B cells was defined. Most importantly, IL-2 was shown to be directly mitogenic for and to expand subpopulations of peripheral blood cells, termed lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). A number of pathologies of IL-2 production or activity have been defined, including Hodgkin's disease, graft versus host disease, systemic lupus erythematosus, lepromatous leprosy, acquired immune deficiency syndrome, and adult T cell leukemia. Murine and human in vivo studies reviewed here have revealed significant parameters of the therapeutic potential as well as the toxicity of this growth factor. Finally, the modulation of IL-2 receptors on human PBL's by thymosin fraction 5 and thymosin alpha 1 suggests that it might be possible to up-regulate IL-2 receptor expression in certain disease states and thus increase the efficacy of IL-2.
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PMID:Recent advances in the understanding of the biochemistry and clinical pharmacology of interleukin-2. 354 63


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