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)

Mouse IgG2a and IgG3 antibodies directed to the human T-cell receptor/CD3 complex stimulate peripheral blood mononuclear cells in almost all individuals. By contrast, responder and non-responder individuals exist for the stimulatory effect of mouse IgG1 and IgG2b antibodies. Whereas responsiveness to IgG1 antibodies is rather frequent (60-70%) and is known to be determined by an Fc gamma RII polymorphism on the accessory cells, little is known about the underlying factors of the rare (6%) IgG2b responsiveness. In this study it is shown that (1) IgG2b responsiveness is genetically determined with a dominant pattern of inheritance; (2) IgG2b responsiveness is determined by a radioresistant feature of responder accessory cells which can be substituted by artificial cross-linking, but not by IL-1 beta or IL-2; (3) stimulation of peripheral blood mononuclear cells of an IgG2b responder by IgG2b antibodies requires rather high antibody concentration compared with stimulation by IgG2a antibodies; (4) the stimulation leads to proliferation and IL-2 receptor expression, but no measurable IL-2 production; (5) antibody binding to known Fc gamma receptors (Fc gamma RI, Fc gamma RII, Fc gamma RIII) is not involved in the stimulatory effect of the IgG2b antibodies in responders. These results demonstrate that responsiveness to IgG2b antibodies against the TcR/CD3 complex depends on a genetically determined feature of accessory cells that is not identical with any of the known Fc gamma receptors. Most likely, the stimulatory effect observed in IgG2b responders is explained by a low grade cross-linking of the antibody by a not yet identified polymorphic structure on the surface of accessory cells.
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PMID:Responsiveness for mouse IgG2b antibodies to the human alpha/beta T-cell receptor/CD3 complex: evidence for genetic determination and low grade antibody cross-linking not mediated by known Fc gamma receptors. 844 19

Cancer patients undergoing interleukin (IL)-2-based immunotherapy frequently experience dose-limiting side effects believed to be caused by the actions of such cytokines as IL-1 beta, tumor necrosis factor (TNF)-alpha and -beta, and interferon-gamma (IFN-gamma). Human peripheral blood mononuclear cells (PBMC) or monocyte-depleted peripheral blood lymphocytes were stimulated for up to 7 days by either of 2 IL-2 analogues (R38A or F42K) that bind to the intermediate-affinity IL-2 beta gamma receptor but have reduced abilities to bind the high-affinity IL-2 receptor. We previously reported that these IL-2 analogues retain the ability to generate lymphokine-activated killing by PBMC. In this study, we analyzed the cytokine content of supernatants from stimulated PBMC and peripheral blood lymphocyte cultures by enzyme-linked immunosorbent assay. The secretions of IL-1 beta, TNF-alpha, and -beta, and IFN-gamma induced by either R38A or F42K were markedly reduced compared with secretions produced in response to recombinant wild-type IL-2. In 4 experiments, secretion was reduced an average of 39% for IL-1 beta, 57% for TNF-alpha, 83% for TNF-beta, and 86% for IFN-gamma. Polymerase chain reaction analysis of recombinant wild-type IL-2 or analogue-stimulated PBMC did not reveal the presence of IL-2 mRNA; thus, differential production of endogenous IL-2 could not account for these findings. These data suggest the interaction of IL-2 and the high-affinity IL-2 receptor on human PBMC or peripheral blood lymphocyte is required for maximal secretion of IL-1 beta, TNF-alpha, TNF-beta, and IFN-gamma. Because such cytokines are believed to mediate the toxicity seen with IL-2-based immunotherapies, IL-2 analogues with reduced binding to the high affinity IL-2 receptor may prove to be an effective and less toxic means of cancer treatment.
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PMID:Human interleukin 2 analogues that preferentially bind the intermediate-affinity interleukin 2 receptor lead to reduced secondary cytokine secretion: implications for the use of these interleukin 2 analogues in cancer immunotherapy. 849 22

The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.
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PMID:Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. 850 May 19

Some evidence points towards a possible autoimmune role in the aetiology of schizophrenia. Experimental findings provide contradictory results regarding abnormalities in cytokine production in this disorder. In the present study we tested the production of cytokines in CSF and serum in 16 schizophrenic patients and 10 healthy controls (tumor necrosis factor alpha - TNF alpha; interleukins IL-1 beta, IL-2, IL-6, soluble IL-2 receptor). Cytokine levels were evaluated by radioactively-labeled antibodies (IL-1 beta, IL-2, IL-6), by enzyme-linked immunoassay (TNF) and by a sandwich enzyme immunoassay (soluble IL-2 receptor). No significant differences were found in either CSF fluid or serum levels of TNF and IL-2 or IL-6. Interleukin-1 beta was significantly decreased in patients' CSF and serum as compared to controls. Soluble interleukin-2 receptor levels were decreased in CSF of patients, but highly increased in their serum in comparison with controls. Changes in various cytokine levels in CSF fluid and serum of schizophrenic patients probably reflect interrelated process of growth, degeneration or neuroimmunological abnormalities, which may all play a role in the pathophysiology of schizophrenia. The present study supports evidence for change in immune activation, probably of peripheral origin, in schizophrenic patients.
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PMID:Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients. 856 79

In this study, we have investigated cytokine (IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, TNF-alpha) and T cell surface molecule (IL-2 receptor, CD28, CTLA-4) gene expression in two way mixed lymphocyte cultures (MLC) enhanced by concanavalin A (ConA) to assess whether this is a useful predictive method for severe graft-versus-host disease (GVHD) and graft failure in allogeneic bone marrow transplantation (allo BMT) patients. Our present study revealed increased mRNA expression of IL-2, IL-5 and IFN-gamma using this assay in patients with delayed engraftment followed by graft failure and patients who developed grade III acute GVHD. Elevated IL-2 and IFN-gamma levels in MLC medium were also observed in these patients. Concerning T cell surface molecule gene expression in our modified MLC, IL-2 receptor gene expression was not altered so much in allo BMT patients, however, CD28 and CTLA-4 gene expression were elevated in patients with graft failure and severe acute GVHD. The elevated expression of cytokines (IL-2, IL-5 and IFN-gamma) and T cell surface molecules (CD28 and CTLA-4) mRNA in our modified MLC, in patients who developed severe lethal transplantation-related complications may suggest an important role for these molecules in inducing a strong alloresponse. Therefore, the detection of increased gene expression of those molecules, in our modified MLC system, appeared to be useful for predicting transplantation-related complications in allo BMT patients. In addition, this modified MLC assay may also be useful for the selection of the most compatible related and unrelated donors.
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PMID:Transplantation-related complications predicted by cytokine gene expression in the mixed lymphocyte culture in allogeneic bone marrow transplants. 857 69

Investigative attempts to identify novel therapy for inflammatory connective tissue diseases continue to evolve. Amiprilose hydrochloride (amiprilose HCl) is a synthetic carbohydrate shown to have anti-inflammatory effects in animal models of inflammatory arthritis and in a multicenter clinical trial. Interleukin-1 (IL-1) is an important mediator of immune regulation, inflammation and joint destruction in arthritis. In the present study, the effects of amiprilose HCl on IL-1 activity, production and receptor distribution were investigated. Drug effects on IL-2 production and receptor distribution on lymphocytes were also explored. Potential regulation of IL-1 activity was determined by monitoring the effects of amiprilose HCl on IL-1 stimulated proliferation of murine thymocytes and human synovial cells. Inhibitory effects on IL-1 beta and IL-2 production by stimulated human peripheral blood monocytes were measured by ELISA and lymphocyte IL-1 beta and IL-2 receptor distribution were analyzed by flow cytometry. The results from in vitro studies demonstrated that low concentrations of amiprilose HCl (1-100 micrograms/ml) stimulated thymocyte proliferation and enhanced the proliferative response of IL-1 stimulated human synovial fibroblasts. IL-1 beta production in cultures of human peripheral blood monocytes was significantly decreased after exposure of the cultures to varying doses of amiprilose HCl as determined by ELISA. Exposure of mitogen activated human peripheral blood lymphocytes to amiprilose HCl resulted in decreased IL-2 production at high concentrations of drug as compared to control. However, at doses of amiprilose HCl previously found to stimulate thymocyte proliferation (1-10 micrograms/ml), increased levels of culture supernatant IL-2 were observed. No amiprilose HCl mediated changes in lymphocyte IL-1 beta or IL-2 receptor expression were observed. The regulatory effects of amiprilose HCl on cytokines support the potential of this drug as a therapeutic agent for the treatment of inflammatory arthritis.
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PMID:Immunoregulatory effects of a synthetic monosaccharide. 857 39

The serum IL-1 beta, IL-2, IL-4, IL-6, IL-8, TNF-alpha and soluble IL-2 receptor levels were measured, and the presence of anti-Fc gamma receptor (Fc gamma R) antibodies was investigated in the sera of 18 patients with systemic sclerosis (SSc). An increase of TNF-alpha was detected in 8 of the 18 cases. II-1 beta was elevated in all the 18 patients. Both IL-2 and IL-4 were elevated in 7 cases. The IL-6 level was elevated in 17 patients, while IL-8 was increased in all cases. The soluble IL-2 receptor level was elevated in 11 patients. Fc gamma R-specific antibodies were detected in the sera of 6 patients, and there was a significant association between anti-Fc gamma R antibody positivity and IL-4 elevation. The presence of anti-Fc gamma R antibodies may influence several cell functions and may contribute to the remarkable variability of cytokine levels in SSc.
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PMID:Serum cytokine and anti-Fc gamma R autoantibody measurements in patients with systemic sclerosis. 872 84

Interleukin-15 (IL-15) is a novel cytokine that has recently been cloned and expressed. IL-15 interacts with components of the IL-2 receptor and exhibits T-cell stimulating activity similar to that of IL-2. In the present study, we investigated the expression of IL-15 in enriched cultures of human fetal astrocytes and microglia using reverse transcription-polymerase chain reaction (RT-PCR) and immunodetection analysis. Low levels of IL-15 were expressed by unstimulated human fetal astrocytes and microglia, and treatment of astrocytes with interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha) increased the expression of IL-15 at both the mRNA and protein level. Treatment of microglia with IFN-gamma and lipopolysaccharide (LPS) similarly increased IL-15 expression in microglia. These findings suggest that IL-15 produced by human fetal astrocytes and microglia may have a role in T cell-mediated immune responses in the human CNS.
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PMID:Interleukin-15 gene expression in human astrocytes and microglia in culture. 880 52

Experimental autoimmune encephalomyelitis (EAE) in rats is typically a brief and monophasic disease with sparse demyelination. However, inbred DA rats develop a demyelinating, prolonged and relapsing encephalomyelitis after immunization with rat spinal cord in incomplete Freund's adjuvant. This model enables studies of mechanisms related to chronicity and demyelination, two hallmarks of multiple sclerosis (MS). Here we have investigated, in situ, the dynamics of cytokine mRNA expression in the central nervous system (CNS) and peripheral lymphoid organs (lymph node cells and splenocytes) of diseased DA rats. We demonstrate that peripheral lymphoid cells stimulated in vitro with encephalitogenic peptides 69-87 and 87-101 of myelin basic protein responded with high mRNA expression for proinflammatory cytokines; interferon-gamma, interleukin-12 (IL-12), tumour necrosis factors alpha and beta, IL-1 beta and cytolysin. A high expression of mRNA for these proinflammatory cytokines was also observed in the CNS where it was accompanied by classical signs of inflammation such as expression of major histocompatibility complex class I and II, CD4, CD8 and IL-2 receptor. The expression of mRNA for proinflammatory cytokines was remarkably long-lasting in DA rats as compared to LEW rats which display a brief and monophasic EAE. Furthermore, mRNAs for putative immunodownmodulatory cytokines, i.e. transforming growth factor-beta (TGF-beta), IL-10 and IL-4 were almost absent in DA rats, in both the CNS and in vitro stimulated peripheral lymphoid cells, while their levels were elevated in the CNS of LEW rats during the recovery phase. We conclude that the MS-like prolonged and relapsing EAE in DA rats is associated with a prolonged production of proinflammatory cytokines and/or low or absent production of immunodownmodulatory cytokines.
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PMID:Cytokines in relapsing experimental autoimmune encephalomyelitis in DA rats: persistent mRNA expression of proinflammatory cytokines and absent expression of interleukin-10 and transforming growth factor-beta. 882 81

This study was designed to investigate changes in the immune system of elite swimmers compared with well-conditioned age- and sex-matched controls in relation to a competition swim (field study). Furthermore, the aim was to reveal possible differences in immune system changes depending on the type of sport performed by comparing with an earlier study of similar design, from the same laboratory that tested elite runners in relation to a competition run. The swimmers were tested before, immediately after and 2 h and 24 h after a competition swim. Lymphocyte subsets (CD5, CD3, HLA-DR, CD4, CD8, CD19, CD3/CD16+56, CD57, CD18, CD16/CD122) all increased after the run, decreased to normal or subnormal levels after 2 h, and returned to normal after 24 h (absolute numbers). The findings were identical for the swimmers and the age- and sex-matched control group. No change in polymorphonuclear granulocyte migration was found. The lymphocyte proliferative responses decreased 2 h after the exercise. No changes were seen in plasma cytokine levels (interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) in relation to exercise, but significantly lower baseline values for IL-6 were observed in the swimmers. An increase in total natural killer cell activity immediately after exercise, followed after 2 h by a decrease, was seen in both swimmers and controls. Finally, no complement activation was detected. Compared with an earlier study of elite runners, differences were seen in granulocyte chemotactic response, TNF-alpha plasma activity and the lymphocyte proliferative response to mitogen. These differences might be explained by the degree of immune system activation following muscle damage during exercise, inducing an increase in cytokines, which are known to activate and modulate both lymphocytes and granulocyte function. Our findings demonstrate identical exercise-induced, immune system changes in elite swimmers and well conditioned controls, and furthermore, the findings suggest that different types of sport performed at maximum intensity induce different immune system changes.
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PMID:Short-term changes in the immune system of elite swimmers under competition conditions. Different immunomodulation induced by various types of sport. 882 44


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