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)

Inflammatory bowel disease (IBD) may be an immunologically mediated disorder in which T cells are unable to respond appropriately to cell surface-associated antigens. To test this possibility, 37 patients with IBD, 24 with Crohn's disease and 13 with ulcerative colitis who were not being treated with immunosuppressive therapy were studied. The ability of T cells to proliferate in response to autologous or allogeneic cells, i.e., the autologous or allogeneic mixed-lymphocyte reaction (MLR) was tested. The autologous MLR was depressed using patient cells compared to control cells, regardless of disease type or activity (1564 +/- 223 cpm versus 3300 +/- 381 cpm, P less than 0.05) while the allogeneic MLR was depressed in patients with active disease only (29,833 +/- 2871 cpm versus 46,799 +/- 3340 cpm, P less than 0.01). The ability of T cells to recognize and lyse allogeneic cells, allogeneic cell-mediated lympholysis (CML), was also low in patients with active disease (24 +/- 4% versus 37 +/- 3%, P less than 0.05). Since T-cell proliferation and cytotoxicity depend upon adequate production of and response to a T-cell growth factor, interleukin 2 (IL-2), IL-2 production and responsiveness in IBD were studied. IL-2 production by patient T cells in response to phytohemagglutinin was only 39% of control values, P less than 0.05. The response to IL-2 was measured by the increase in T-cell proliferation in the autologous MLR in medium alone or medium supplemented with IL-2. Control T-cell proliferation rose from 3300 +/- 381 cpm to 10,761 +/- 428 cpm with exogenous IL-2 (P less than 0.001). Patient T-cell proliferation rose from 1564 +/- 223 cpm to 6817 +/- 771 cpm with IL-2 (P less than 0.001) but did not reach the level of the IL-2-supplemented control autologous MLR (P less than 0.05). In addition, the percentage of activated patient T cells having Tac antigen (IL-2 receptor) was depressed (P less than 0.05). These findings did not vary with disease type or activity. It is concluded from these data that peripheral blood T lymphocytes from patients with IBD have a diminished response to cell surface antigens which is associated with a decrease in IL-2 production and receptor generation. These defects may be responsible for the depressed T-cell proliferation and cytotoxicity that accompany IBD.
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PMID:T-cell abnormalities in inflammatory bowel disease are mediated by interleukin 2. 623 13

We have previously shown that the expression of alpha-fetoprotein (AFP) receptors is impaired in mitogen-activated peripheral blood mononuclear cells (PBMCs) from HIV+ individuals and that this novel abnormality reflects an unusual proliferation response of PBMCs to mitogenic stimuli. Here we comparatively analyze, in PBMCs from patients with AIDS and related syndromes, (1) changes in membrane fluidity, measured as the cholesterol/phospholipid ratio (CH/PL), and (2) changes in the expression of AFP receptors and of the alpha chain of IL-2 receptor (TAC antigen). Relative to normal cells, the expression of AFP and IL-2 receptors appeared considerably reduced in AIDS-related complex (ARC) and AIDS patients. In asymptomatic HIV+ individuals the amount of AFP receptors was within the normal range, whereas that of IL-2 receptors increased twice. CH/PL ratios were significantly lower in PHA-activated than in quiescent PBMCs from healthy donors, which implies a gain in membrane fluidity. For seropositive groups, no statistically significant changes in CH/PL ratios were appreciated on PHA activation. Nevertheless, in HIV+ asymptomatic individuals, the CH/PL ratio of quiescent PBMCs resembled that of PHA-activated PBMCs from healthy donors, suggesting that quiescent PBMCs are in a partially activated or "preactivated" status. With the worsening of the disease, toward ARC and AIDS stages, however, quiescent PBMCs from these groups showed a considerable loss in membrane fluidity, evidenced by elevated values of the CH/PL ratio. This radical change strongly suggest a severe alteration of the lipid metabolism in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of alpha-fetoprotein and interleukin 2 receptors and impairment of membrane fluidity in peripheral blood mononuclear cells from AIDS and related syndromes. 752 36

Cytokines produced by T lymphocytes, monocytes/macrophages, and fibroblasts play a central role in the immune response and in the development of graft-versus-host disease (GVHD). Also, it has been reported that dysregulated production of cytokines maybe the primary mediator of clinical manifestation of acute GVHD. Regarding cytokine gene expression after human allogeneic bone marrow transplantation (allo BMT), we have demonstrated increased IL-1 beta, IL-6, and TNF-alpha mRNA expression in peripheral blood mononuclear cells during the development of acute and chronic GVHD and that the degree of the increase was dependent on the severity of the disease. Furthermore, overexpression of these cytokine mRNAs could be detected before the clinical manifestations of GVHD developed. In contrast, IL-2 mRNA expression was not detected in peripheral blood mononuclear cells in GVHD patients. On the other hand, we have reported that increased mRNA expression and protein product of IL-2 and IFN-gamma were evident in the mixed lymphocyte culture of the cases who developed severe lethal transplantation-related complications. Therefore, the detection of increased IL-2 and IFN-gamma gene expression in MLC appeared to be useful for predicting transplantation-related complications in BMT patients. Furthermore, we found increased IL-2 receptor alpha subunit mRNA expression in the peripheral blood mononuclear cells during GVHD. These findings may indicate the important role of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha in the development of the clinical manifestation of GVHD and also may be indicative of the important role of IL-2 and the IL-2 receptor in allo response perhaps mainly as an autocrine effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine gene expression after allogeneic bone marrow transplantation. 778 51

Peripheral blood mononuclear cells from patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and heterosexual controls were stimulated with anti-CD3 monoclonal antibody, phorbol myristate acetate (PMA), or both and 3H thymidine incorporation and IL-2 receptor (IL-2R alpha; CD25; Tac antigen) expression were measured. In addition, basal plasma membrane potential and plasma membrane potential following anti-CD3 stimulation were compared between the three groups. A significantly reduced DNA synthesis and CD25 expression was observed in both AIDS and ARC upon stimulation with anti-CD3 or PMA. Although, a significant synergism was observed with anti-CD3 plus PMA stimulation in both AIDS and ARC, and the responses were normalized to the levels of anti-CD3 or PMA response in normal control, the levels were significantly lower than those observed with anti-CD3 plus PMA in controls. Plasma membrane potentials were decreased (membrane depolarized) in both ARC and AIDS (AIDS > ARC), and anti-CD3 had no effect on further depolarization of plasma membrane in AIDS. These data suggest a defect in signal transduction pathway in patients with HIV-1 infection.
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PMID:Signal transduction defect in the acquired immunodeficiency syndrome and AIDS-related complex. 820 99

A detailed analysis of the immune system response has been performed during the development and progression of dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. For this aim, a number of immune parameters (thymocyte and splenocyte proliferative response to T-dependent mitogens, antibody production, lymphocyte subset phenotyping, interleukin 2 receptor expression in resting and activated lymphocytes, thymus morphology and morphometry), were correlated with tumor appearance and growth at different (-7, 0, +15, +30, +60, +90, and +120 days) time intervals after intragastric administration of DMBA, in the absence or the presence of a concomitant treatment with the thymic pentapeptide thymopentin (TP5). A profound and time-dependent immunosuppression characterized the treatment with the carcinogen. Both cell-mediated and humoral immune responses showed a 50% inhibition 2 weeks after DMBA administration, with a peak after 30 days, followed by a plateau until 120 days of observation. The mechanism responsible for reduced ability of thymocytes and splenocytes to respond to both Con-A and PHA was explained by the significant inhibition of one of the key steps of T cell activation, namely the expression of IL-2 receptor in lymphocytes from DMBA-treated animals. The flow cytometric analysis of lymphocyte subpopulations revealed an important reduction in the overall populations of thymocytes and splenocytes. At the thymus gland level, a dramatic reduction of double positive CD4+CD8+ and a decrease of CD4+CD8- and CD4-CD8+ were observed, together with a marked atrophy of the thymic cortex, and impairment of the thymic microenvironment. One hundred and twenty days after DMBA administration, approximately 60 to 70% of the animals developed tumors with a mean tumor surface area of 2.88 +/- 0.86 cm2, and a number of 2.44 +/- 1.0. Treatment with TP5 (100 ng/animal, three times a week, starting a week before DMBA), produced specific effects on different immune compartments and tumoral growth, characterized by a significant reversal of immune depression with a stimulatory effect measured on lymphoproliferative assays, lymphocyte subset distribution, and IL-2 receptor expression. Moreover, thymic atrophy was almost completely prevented in TP5 treated animals. Of major interest, a significant delay in the appearance and growth of tumors was observed in TP5 treated rats. When DMBA-treated animals were followed for the entire observation period (0-120 days) and the immune responsiveness correlated according to tumor progression, stability, or regression, a positive correlation was calculated between the degree of immune system depression and the individual rate of tumor growth; in TP5-treated rats the majority of the tumors were static or regressing tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The immune system response during development and progression of carcinogen-induced rat mammary tumors: prevention of tumor growth and restoration of immune system responsiveness by thymopentin. 831 80

Melanoma cells can secrete several cytokines and express various cell surface molecules, such as the intercellular adhesion molecule ICAM-1, class II histocompatibility antigens, and the CALLA antigen, typically found in cells of the immune system. We have investigated the possible expression of interleukin-2 (IL-2) receptors in melanoma using monoclonal antibodies specific for the p55/alpha chain (TAC antigen) and the p75/beta subunit. Flow cytometric analysis of cultured melanoma cells showed the presence of low levels of the TAC antigen and of the beta chain on the surface of several cell lines. Similar results were obtained in vivo by immunohistochemistry on cryosections prepared from cutaneous and ocular melanoma explants. Positive staining was observed for the alpha chain of the IL-2 receptor in a high percentage of tumour cells. The beta chain could also be detected, although in a limited number of specimens. Analysis of RNA from melanoma cell lines by Northern blot showed the presence of typical 4 Kb transcripts for the p75 subunit, while low-abundance message for the p55 chain could be detected using combined reverse transcription/polymerase chain reaction analysis. Together, these results suggest that melanoma cells may express high affinity receptors for IL-2.
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PMID:Expression of IL-2 receptors in human melanoma cells. 831 84

We isolated a cDNA clone for the gamma chain of the mouse interleukin 2 receptor. Introduction of the mouse gamma chain cDNA clone into a mouse fibroblast cell line, L929, expressing the mouse alpha beta heterodimer IL-2 receptor converted pseudo-high affinity of the IL-2 receptor into functional high, resulting in internalization of IL-2 and induction of the c-myc, c-fos and c-jun genes. The mouse beta gamma heterodimer, however, failed to bind IL-2 unlike the human beta gamma heterodimer intermediate-affinity receptor. These results indicate that the mouse functional IL-2 receptor is a complex comprising three distinct subunits, alpha, beta and gamma chains, but the beta gamma heterodimer is not functional and different from the human heterodimer.
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PMID:Cloning of the mouse interleukin 2 receptor gamma chain: demonstration of functional differences between the mouse and human receptors. 850 26

The aim of the study was to investigate whether a regular moderate endurance exercise programme influenced the in vitro cytokine synthesis by stimulated whole blood cultures. To this end, eight healthy subjects exercised moderately by running for 3-5 h a week over a period of 12 weeks, whilst seven other healthy subjects served as the control group. The intensity of the exercise was determined by lactic acid concentrations in the blood which were maintained between 1.8 and 2.5 mmol x l(-1). Over the period of training the running velocity producing the 4 mmol x l(-1) lactic acid threshold increased from 2.86 (SD 0.83) m x s(-1) to 3.06+/-0.79 m x s(-1) (P < or = 0.008). Blood samples were taken at rest before and after the training programme. The following blood parameters were determined: leucocyte count, differential leucocyte count, lymphocyte subpopulations [CD14 positive (+)/CD45+, CD4+/ CD25+, CD8+, CD16+/CD122+]. Whole blood cultures were stimulated with lipopolysaccarides [interleukin (IL)-1 beta and IL-6] and staphylococcal enterotoxin B [IL-2, soluble interleukin 2 receptor (sIL2-R) and interferon (IFN)-gamma]. Cytokine concentrations in the supernatants were measured using an enzyme-linked immunosorbent assay. The white blood cell count, differential leucocyte count, lymphocyte subset distribution and the expression of the CD25 and CD122 antigen on lymphocytes were unchanged by training. After the training programme the IL-1 beta production changed significantly [1496 (SD 264) pg ml(-1) before, compared to 2127 (SD 672) pg ml(-1) after training, P < or = 0.008]. In the control group these parameters remained unchanged. With respect to changes in the values in both groups the syntheses of IL-1 beta (P < or = 0.023) and IL-6 (P < or = 0.021) were significantly higher after regular training. The syntheses of IL-2, sIL-2 and INF-gamma were not significantly influenced. Regular endurance exercise influenced the in vitro production of monocyte derived cytokines, while the effect of exercise on the cytokines synthesized by T-cells appeared to be of lesser importance.
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PMID:Increased concentrations of interleukin 1-beta in whole blood cultures supernatants after 12 weeks of moderate endurance exercise. 1034 59

Interleukin-2 (IL-2) specifically recognizes high-mannose type glycans with five or six mannosyl residues. To determine whether the carbohydrate recognition activity of IL-2 contributes to its physiological activity, the inhibitory effects of high-mannose type glycans on IL-2-dependent CTLL-2 cell proliferation were investigated. Man(5)GlcNAc(2)Asn added to CTLL-2 cell cultures inhibited not only phosphorylation of tyrosine kinases but also IL-2-dependent cell proliferation. We found that a complex of IL-2, IL-2 receptor alpha, beta, gamma subunits, and tyrosine kinases was formed in rhIL-2-stimulated CTLL-2 cells. Among the components of this complex, only the IL-2 receptor alpha subunit was stained with Galanthus nivalis agglutinin which specifically recognizes high-mannose type glycans. This staining was diminished after digestion of the glycans with endo-beta-N-acetylglucosaminidase H or D, suggesting that at least a N-glycan containing Man(5)GlcNAc(2) is linked to the extracellular portion of the IL-2 receptor alpha subunit. Our findings indicate that IL-2 binds the IL-2 receptor alpha subunit through Man(5)GlcNAc(2) and a specific peptide sequence on the surface of CTLL-2 cells. When IL-2 binds to the IL-2Ralpha subunit, this may trigger formation of the high affinity complex of IL-2-IL-2Ralpha, -beta, and -gamma subunits, leading to cellular signaling.
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PMID:Interleukin-2 carbohydrate recognition modulates CTLL-2 cell proliferation. 1107 50

Expression of the alpha chain of the interleukin 2 receptor on T lymphocytes is restricted, increasing in the setting of activation, particularly after antigenic stimulation via the TCR. The effects of IL-2 in vitro on the expression of CD25 and proliferation as well as the cytokine induction in CD25-depleted T cells were studied. CD25-depleted and PBMC of healthy donors were cultured for 7 days with 0, 10, or 100 IU/ml of IL-2. Phenotypic analysis and measurement of cytokines in the culture supernatants were performed. IL-2 led to a dose-dependent induction of the IL-2R alpha chain on both CD4 and CD8 T lymphocytes. In the CD25-depleted cultures, IL-2 treatment (100 IU/ml) increased the percentage of CD4 T cells expressing CD25 by 30.6% (P = 0.05) and of CD8 T cells by 48.2% (P = 0.01) on day 7 compared to no treatment. In the PBMC cultures the increase on day 7 was 36.4% for CD4 (P = 0.01) and 50.8% (P = 0.025) for CD8 T lymphocytes. The patterns of cytokine induction in the CD25-depleted and control cultures were similar with increases of IFN-gamma, GM-CSF, IL-16, TNF alpha, and soluble IL-2 receptor in the IL-2-containing cultures. CFSE experiments demonstrated the proliferative capacity of both CD25-positive and -negative T cells. Interleukin 2 alone can lead to a dose-dependent induction of the alpha chain of its receptor on resting CD4 and CD8 T lymphocytes. IL-2 as a sole stimulant is also associated with generation of a cytokine milieu that includes IFN-gamma, GM-CSF, IL-16, and TNF alpha.
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PMID:Interleukin 2 leads to dose-dependent expression of the alpha chain of the IL-2 receptor on CD25-negative T lymphocytes in the absence of exogenous antigenic stimulation. 1111 66


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