Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nocardia rubra cell wall skeleton (N-CWS) was found to synergistically augment lymphokine-activated killer (LAK) cell generation from human peripheral blood mononuclear cells (PBMC) in the presence of a suboptimal dose of recombinant interleukin-2 (rIL-2). N-CWS increased the number of PBMC expressing IL-2 receptor on their surfaces, and the presence of N-CWS at the early stage of the culture period was essential for the exertion of its augmentative activity on the LAK induction. The predominant phenotype of LAK precursor cells responding to N-CWS and rIL-2 was CD3- CD16+. Culture supernatant from N-CWS-stimulated PBMC was found to act as a substitute for N-CWS in the induction of LAK generation in the presence of rIL-2, suggesting that these cells produced a factor capable of augmenting LAK cell induction (LAK helper factor, LHF). LHF was found to have a molecular mass of 29 kDa by gel filtration, and could also function as a killer helper factor to augment allo-antigen-specific cytotoxic T lymphocyte generation from human peripheral blood T cells as well as murine thymocytes. LHF showed no species specificity, indicating that it is different from IL-4. The enhancing activity of LHF was not neutralized with anti-TNF alpha, anti-IL-1 alpha, or anti-IL-1 beta antibodies. Furthermore, no tumor necrosis factor-alpha (TNF alpha), TNF beta, IL-1 alpha, beta, IL-2, IL-5, IL-6 or interferon activity was detected in semi-purified LHF during enzyme-linked immunosorbant assay and biological assays. The present findings indicate that LHF produced from N-CWS-stimulated PBMC is a molecule distinct from TNF alpha, TNF beta, interferon, IL-1, -2, -4, -5, and -6, and suggest that LHF might be a novel lymphokine involved in LAK generation.
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PMID:Augmentative effect of Nocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s). 259 89

A series of experiments examined effects of stressful conditions on several cellular immune responses and attempted to elucidate the physiological mechanisms underlying these effects. Initial studies showed that stressful conditions can profoundly suppress immune responses of blood and splenic lymphocytes, including T-cell mitogenesis, natural killer cell activity, production of interleukin-2 (IL-2) and interferon and IL-2 receptor expression. Subsequent studies found that (1) multiple physiological pathways mediate stress-induced suppression of these responses; (2) stress-induced suppression of these responses is produced, at least in part, by a peptide with molecular weight greater than 10 kilodaltons, which stressed animals release into circulation; (3) whereas most stressful conditions suppress immune responses, stressful conditions of moderate intensity can enhance cellular immune responses; and (4) extremely small quantities of interleukin-1 (IL-1) acting in the brain (e.g., 3.1-12.4 X 10(-15) moles) bring about suppression of cellular immune responses very rapidly and for a prolonged period of time. The relationship between the newly-discovered immunosuppressive influence of IL-1 in the brain and immunosuppression produced by stressful conditions remains to be determined.
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PMID:Behavioral and neural influences on cellular immune responses: effects of stress and interleukin-1. 265 30

The current study analyses the ultramorphology, lymphocyte activation marker expression, DNA synthesis, and gamma-interferon and immunoglobulin production of inflammatory cells in oral lichen planus (OLP) lesions. According to these four different aspects of lymphocyte activation, only a minor fraction, 5% at the most, of all T cells in situ were activated. However, it is this minor fraction, and not the resting T cells without signs of activation, which may prove decisive for the outcome of the local immune-inflammatory process in OLP. We also studied both spontaneous and phytohaemagglutinin (PHA) stimulated peripheral blood T cell function. 3H-thymidine incorporation and gamma-interferon secretion were determined. Interleukin-2 (IL-2) receptor and major histocompatibility complex (MHC) locus II coded la antigen were stained with monoclonal antibodies. The peripheral blood T cell subsets and spontaneous MHC locus II antigen expression were similar in OLP patients and healthy controls, whereas spontaneous lymphocyte proliferation was lower in OLP patients (p less than 0.01). The PHA induced expression of IL-2 receptor and T cell proliferation were similar in both groups. Gamma-interferon secretion and MHC locus II antigen expression were low in OLP patients compared with the controls (p less than 0.01). The results suggest a defect in OLP T cell activation disclosed by in vitro PHA stimulation and occurring between IL-2 receptor ligand binding and gamma-interferon secretion. The findings of our peripheral blood mononuclear studies do not, however, provide an easy or straightforward explanation of the changes observed in the disease itself, particularly with respect to local pathogenesis.
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PMID:Lymphocyte activation in oral lichen planus. 266 69

Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.
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PMID:Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy. 278 85

The role of interferon (IFN)-gamma in the activation of human T cells was investigated. Addition of IFN-gamma to mixed-lymphocyte cultures (MLC) augmented both the proliferation and the development of T-cell-mediated cytotoxicity. IFN-gamma also augmented the early expression on CD8+ but not CD4+ lymphocytes of IL-2 receptor alpha chain (Tac antigen) and Class II major histocompatibility antigen (HLA-DR). This effect synergized with that caused by interleukin 2 and was not observed with IFN-alpha. The addition of neutralizing antibody against IFN-gamma to MLC suppressed the development of cytotoxicity and proliferation and the expression of activation antigens on CD8+ cells. In experiments in which highly purified CD8+ T cells were activated with cell-free stimuli, IFN-gamma slightly but significantly augmented proliferation, antibody to IFN-gamma suppressed proliferation, and excess IFN-gamma reversed this suppression. It is concluded that (i) IFN-gamma augmented activation of T cells in human MLC, (ii) IFN-gamma exerted effects directly on T cells, and (iii) IFN-gamma preferentially augmented CD8+ cell activation.
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PMID:Effects of interferon-gamma on the activation of human T lymphocytes. 282 98

To understand molecular mechanisms of clonal expansion of lymphocytes we have isolated cDNA clones for two lymphokines, interleukins (IL) 4 and 5 that induce proliferation and maturation of B-lymphocytes. Structures of IL-4 and IL-5 revealed a remote homology with other lymphokines such as IL-3 and gamma-interferon. IL-4 and IL-5 were shown to affect not only B-lymphocytes but also T-lymphocytes and several other cells derived from bone marrow stem cells. We have also studied the structure and function of the IL-2 receptor: our focus was the molecular basis for the high and low affinity states of the receptor encoded by the identical cDNA. We propose the affinity conversion model that the high-affinity state of the IL-2 receptor is a ternary complex of IL-2, the IL-2 receptor, and a postulated "converter protein", which is fewer in number than the receptors.
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PMID:Growth factors and receptors of lymphocytes. 283 74

HIV infection induces both immune deficiency and immune stimulation. Central to the pathology of HIV infection is reduction in the numbers and function of CD4 T cells. Impaired functions include decreased proliferation, IL-2 receptor expression and production of lymphokines (IL-2 and gamma interferon (IFN]. HIV infection stimulates B cells and CD8 T cells. This is seen relatively soon after HIV infection. Increased activation and immaturity are seen in both these cell groups. In vitro studies confirm HIV stimulation of these cells. Studies have been conducted on patients with AIDS and opportunistic infection (OI) or Kaposi's sarcoma (KS), with AIDS-related complex (ARC) or with persistent generalized lymphadenopathy (PGL), as well as on asymptomatic HIV-seropositive and -seronegative homosexually active men. The latter group has been followed at 6-month intervals for the past 2-3 years. Those who seroconverted (became HIV-infected) were studied to investigate early changes following HIV infection. To delineate the immunopathology of infection with HIV, serial testing of seropositive individuals was carried out to determine the rate of CD4-T-cell reduction. Lowered CD4-T-cell number and percentage and CD4/CD8 ratio correlate with the occurrence of AIDS and with survival after AIDS-KS diagnosis. Seropositive individuals, however, differed markedly in the rate of CD4-T-cell reduction; in some, no reduction in CD4 cells occurred over a two-year period of observation. We propose that, in individuals in which CD4 levels have reached a plateau, effective host resistance to further CD4 cytoreduction has occurred.
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PMID:Immune pathogenesis of AIDS and related syndromes. 295 95

A recently established thymic stroma-derived cell line (TSCL) supported the growth of the interleukin (IL) 2-dependent, antigen-specific helper T cell (Th) clone, 9-16, without requirement for IL-2 and antigen, and such growth was substituted by a factor produced into cultures by this established TSCL. This substance, thymic stroma-derived T cell-growth factor (TSTGF), was capable of inducing the proliferation of various Th clones including 9-16 Th clone, but not of cytotoxic T cell clones. TSTGF-induced growth promotion was obtained in a dose-dependent fashion and in maintaining antigen specificity of Th clones. The culture supernatant from the TSCL did not contain detectable level of IL-1, IL-2, IL-3, IL-4, or interferon activity. The proliferation of 9-16 Th clone was stimulated by recombinant IL-2 and IL-4 as well as TSTGF, but not by IL-1, IL-3, or interferons. However, the proliferation of this Th clone by IL-2 or IL-4 was almost completely inhibited by anti-IL-2 receptor or anti-IL-4 monoclonal antibody, respectively, whereas TSTGF-induced growth of 9-16 Th clones was not affected by either type of antibody, demonstrating that TSTGF is functionally distinct from IL-2 and IL-4. In addition, TSTGF activity was also obtained from the culture supernatant of the primary thymic explant, which was freshly prepared. These results indicate that the primary thymic explant as well as an established TSCL produce factors capable of promoting the growth of helper but not cytotoxic type of T cells in the absence of T cell growth factors thus far defined.
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PMID:Thymic stroma-derived T cell growth factor (TSTGF). I. Functional distinction of TSTGF from interleukins 2 and 4 and its preferential growth-promoting effect on helper T cell clones. 295 57

The antirejection eicosanoids--PGE2, (PGD2), and PGI2--have an attenuating effect on T-cell proliferation by inhibition of IL-1, IL-2, and class II antigen expression on macrophages, and the prorejection eicosanoids--TXA2, LTB4, LTC4, and LTD4--enhance T-cell proliferation. LTB4 stimulates IL-1 and IL-2 formation and expression of IL-2 receptor. The mechanism of enhancement of T-cell proliferation by TXA2 has not been demonstrated. LTC4 and LTD4 promote gamma-interferon release and can replace IL-2 as a stimulator of gamma-interferon. PAF at high concentrations inhibits lymphocyte proliferation. The eicosanoids interfere with the same mechanisms as CsA and corticosteroids on T-cell clonal expansion. In experimental organ transplantation, corticosteroids can be replaced by compounds preventing the formation or expression of the prorejection eicosanoids or analogs of antirejection eicosanoids as well as by PAF antagonists. In addition, these drugs exert synergistic effect with CsA and azathioprine.
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PMID:Leukotrienes, thromboxane, and platelet activating factor in organ transplantation. 295 38

A 57-year-old man with a history of recurrent infections from the age of 50 was hospitalized with a diagnosis of common variable hypogammaglobulinemia (CVH). Immunological studies revealed a severe reduction of circulating immunoglobulins of all classes. Immunophenotyping of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies, revealed normal values of total B and T cells with CD4/CD8 ratio sharply reduced (0.35) as compared to normal (1.6) because of an increase of CD8 and a decrease of CD4 cells. The surface expression of IL-2 receptor was normal. Natural cytotoxic and phagocytic system presented several abnormalities: a deep impairment of NK activity was found in spite of a normal number of NK cells, as ascertained by Leu 19 and B73.1 monoclonal antibodies. The defective NK activity was not restored by interferon alfa, but was normalized by recombinant IL-2. Phagocytic function, as defined by zymosan-stimulated O2- production was almost absent. The involvement of natural cytotoxic and phagocytic systems in CVH has been rarely reported; the possible causative role of a chronic viral infection (Epstein-Barr virus?) is discussed, on the base of anamnesis.
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PMID:NK cell activity and monocyte dysfunctions in a patient with common variable hypogammaglobulinemia. 297 23


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