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)

Peripheral blood mononuclear cells (PBMC) from aged humans were found impaired in their ability to mount T mitogen induced proliferative responses and NK cell activity. The production of IL-2 in response to PHA has also been found decreased in the aged subjects. When the data from IL-2 production and cellular responsiveness of aged and young groups were pooled for regression analysis, a significant correlation was found both for mitogenic responses and NK activity. The reduced proliferative responses and NK cell activity can be enhanced by exposing them to exogenous IL-2. However, they were not fully reconstituted to the levels achieved in PBMC of the young subjects supplemented in vitro with IL-2. This would indicate that the reduced cellular responsiveness in aging may be related both to a defect of IL-2 receptor expression on T cells of aged subjects and to an impairment in the endogenous IL-2 synthesis in the aged individuals.
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PMID:Interleukin-2 production and activity in aged humans. 387 17

The effect of cyclosporine A (CyA) on the expression of the Tac-antigen (IL-2 receptor) on PHA-activated PBMNC was analysed by immunofluorescence. In the initial experiments we determined the number of Tac(+) cells, disregarding cell size; we found that CyA did not affect the number of cells expressing the Tac antigen after lectin stimulation (Fig. 1, Table 1). When we found that comparable numbers of Tac(+)-lymphocytes absorbed less IL-2 when grown in CyA as compared to solvent controls, we analysed in more detail the correlation between Tac-antigen expression and cell size of cell populations grown in CyA. It was found that CyA prevented a majority of PHA-activated PBMNC to undergo blastogenesis despite having expressed the IL-2 receptor. A minority of the cells, however, were refractory to the CyA-mediated suppression of blast formation. Studies analysing the Tac antigen expression semiquantitatively showed that CyA reduced the intensity of Tac antigen expression on cells of all sizes.
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PMID:On the partial suppression of IL-2 receptor expression and the prevention of lectin-induced lymphoblast formation by cyclosporine A. 392 57

There are presently no monitoring tools to assess the immunosuppressive effect of cyclosporine (CsA) in vivo, since the mode of drug action is incompletely understood in man. Experimental in vitro studies suggest that CsA causes reversible inhibition of T helper cell generation of interleukin-2 (IL-2). Therefore the present study examined the effect of CsA administered in vivo on the capacity of kidney transplant recipient lymphocytes to generate IL-2 after mitogen (phytohemagglutinin [PHA]) stimulation. IL-2 production was measured by the capacity of lymphocyte supernates to trigger proliferation of a human IL-2-dependent T cell line. Peripheral blood lymphocytes (PBL) from CsA-Pred treated recipients displayed 40.6% inhibition (1.14 +/- 0.06 U/ml, n = 117, P less than 0.001) of IL-2 production compared with normal individuals (1.93 +/- 0.04 U/ml, n = 164). Dialysis patients did not display inhibited IL-2 production. The inhibition of IL-2 generation was observed in patients treated solely with CsA without supplemental corticosteroids (1.24 +/- 0.12 U/ml, n = 25; 35.8% inhibition, P less than 0.001). CsA did not inhibit the expression of the IL-2 receptor: 4.15 +/- 11.2% and 63.1 +/- 10.3 of normal lymphocytes and 36.7 +/- 9.8% and 60.4 +/- 12.2% of CsA-treated patient lymphocytes expressed anti-IL-2 receptors after 24 or 48 hr of PHA stimulation, respectively. Serial posttransplant studies in individual patients confirmed no inhibition of IL-2 generation pretransplant (1.94 +/- 0.07 U/ml) followed by a high degree of inhibition thereafter, namely 0.87 U/ml (55.0% inhibition) at 1 week, 1.15 U/ml (40.6% inhibition) at 2 weeks, 0.42 U/ml (78.2% inhibition) at 3 weeks, and 0.99 U/ml (48.7% inhibition) at 4 weeks. There was a correlation between the occurrence of rejection episodes in the 7 patients who suffered this event, and IL-2 generation by patient PBL. Before pulse therapy there was no inhibition of IL-2 generation (2.39 U/ml; -23.8 inhibition), documenting a poor level of immunosuppression in these patients. At 1, 2, 3, or 4 days after corticosteroid pulse therapy, PBL displayed 39.4%, 57.0%, 50.0% and 49.2% inhibition, respectively. These findings suggest not only that CsA treatment impairs the generation of IL-2 by patient lymphocytes, but also that failure to display this response is associated with a poor level of immunosuppression and allograft rejection. These studies provide a foundation for serial analyses of IL-2 generation, in order to dissect its utility as a pharmacodynamic parameter to assess the level of CsA-induced immunosuppression.
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PMID:Pharmacodynamic assessment of the in vivo cyclosporine effect on interleukin-2 production by lymphocytes in kidney transplant recipients. 393 6

A new method for the determination of both low and high affinity binding sites on interleukin 2 (IL-2) target cells is described, which is based on differential dissociation of the ligand receptor complex. The technique requires highly purified but not radiolabelled IL-2. In the presence of activated charcoal the low affinity binding sites had a dissociation half time of less than 1 min, while that of the high affinity binding sites was 80 min. Human T-lymphocytes expressed both classes of binding sites within 48 h after PHA stimulation. During culture of PHA-stimulated T-lymphocytes, low affinity binding sites appeared on day 2 and remained high until day 8. High affinity binding sites appeared on day 1, were highest on day 2, and remained high until day 6. The changes in the concentration of the high affinity binding sites are considered as being the result of: receptor stimulation by PHA and/or IL-2 (days 1-2); receptor down regulation by extensive IL-2 production (day 3); increase of unoccupied IL-2 receptor after disappearance of IL-2 from the medium (days 4-6) and cessation of receptor synthesis and receptor breakdown (days 7-10).
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PMID:Binding of interleukin 2 to target cells: determination of high and low affinity binding sites on T-lymphoblasts by differential dissociation. 393 57

Human T lymphocyte colonies may be grown in agar from pre-T peripheral blood cells. Pre-T cells giving rise to these colonies represent 0.5% of the non-adherent, E rosette and Leu 1 depleted mononuclear cell subpopulation. T colony formation is induced by PHA stimulation and only if media conditioned by PHA stimulated peripheral blood lymphocytes (PHA-LCM) is added. These media contained interleukin-2 (IL-2) and T colony promoting activity (TCPA) for pre-T cells. TCPA is co-eluted with IL-2 by gel filtration with an apparent molecular weight of 18,000 daltons. Moreover, when PHA-LCM are absorbed on IL-2-dependent cultured T cells, TCPA is removed as well as IL-2. In attempt to further demonstrate the role of IL-2 in T colony formation by the pre-T cells we used the anti-Tac monoclonal antibody directed against IL-2 receptor. We demonstrated that anti-Tac inhibits T colony formation in a dose-dependent manner in pre-T cells. We conclude that IL-2 is the essential exogenous factor contained in PHA-LCM which allows pre-T cell differentiation expression and proliferation in agar medium.
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PMID:The role of interleukin-2 in T colony formation by human pre-T cells (pTCFC). 633 91

Peripheral blood mononuclear cells from 22 pemphigus patients with active disease and 30 normal subjects were evaluated for interleukin 2 (IL-2) production and IL-2 receptor expression following stimulation with phytohemagglutinin P (PHA-P). The IL-2 levels were lower in patients compared to corresponding controls and the production was delayed after PHA stimulation. This deficiency was most pronounced in severely affected patients. IL-2 receptor appearance also was lower after PHA stimulation in a small number of patients tested. These results indicate that some cellular immune functions are altered in pemphigus.
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PMID:Deficiency of interleukin-2 production and interleukin-2 receptor expression on peripheral blood leukocytes after phytohemagglutinin stimulation in pemphigus. 643 16

The majority of patients with Dermatitis Herpetiformis (DH) have a gluten-sensitive enteropathy which may be triggered by a T cell-mediated immune response to gluten. Using a proliferative assay, the responses to gluten fraction III, recall antigens and mitogens of peripheral blood mononuclear cells (PBMC) and gut T cell lines (TCL) isolated from patients with Dermatitis Herpetiformis (DH) and normal controls were studied. In most cases, neither PBMC nor gut T cell lines (which were predominantly CD3+, CD4+, TCR alpha beta +) from either controls or patients proliferated in response to gluten fraction III alone. However, the addition of 10 U/ml IL-2 to PBMC cultures containing gluten fraction III resulted in a marked increase in proliferation in 9/19 DH patients and 7/11 controls compared to IL-2 alone. Furthermore, gluten-induced upregulation of IL-2 receptor (CD25) expression was demonstrated on PBMC from 4/4 patients with DH and 2/3 controls after 7 days' culture with antigen. A similar effect by exogenous IL-2, or the same concentration of IL-4, was observed in 8/11 (P = 0.02) and 5/6 respectively DH, and 3/4 normal gut T cell lines. No difference was observed in the response of DH and control PBMC to Tetanus toxin, Candida albicans and PPD; both normal and DH gut T cell lines were unresponsive to these antigens. However, the addition of IL-2 increased the response to Candida albicans by DH gut T cell lines. Moreover, the response of DH gut T cell lines to PHA (P < 0.001), Concanavalin A and anti-CD3 were markedly reduced compared to PBMC from the same patients. These findings suggest that gluten-specific T cells present in the blood and gut of normal and DH individuals are activated by but do not proliferate in response to specific antigen.
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PMID:Lack of proliferative response by gluten-specific T cells in the blood and gut of patients with dermatitis herpetiformis. 749 50

The cellular and molecular regulation of IL-4 mRNA expression in human tonsillar T lymphocytes was examined to define the mechanisms responsible for biphasic IL-4 mRNA expression in this lymphoid organ. Tonsillar T cells expressed IL-4 mRNA in a biphasic manner with peaks at 8 and 24 h after PHA stimulation. De novo protein synthesis was not required for IL-4 mRNA expression because cycloheximide treatment of tonsillar MNC did not ablate the response. Nuclear runoff assays demonstrated transcription of the IL-4 gene at 8 and 24 h, which was not affected by addition of actinomycin D. Separation of T cells into naive (CD45RAhi/CD29lo) and primed (CD45RAlo/CD29hi) subpopulations revealed that although naive and primed T cells expressed IL-4 mRNA at 8 h, the 24-h peak of IL-4 mRNA expression was solely due to primed (CD45RAlo/CD29hi) Th cells. This effect was tissue specific and IL specific in that 1) primed peripheral blood T cells had only one peak of IL-4 mRNA expression at 8 h and 2) in primed tonsillar T cells, mRNA expression of IL-2, IL-6 and IL-2 receptor and c-myc was not delayed. Thus, IL-4 mRNA expression in the tonsil differs depending on the surface expression of different isoforms of the leukocyte common Ag. The tissue- and stimulus-specific regulation of IL-4 mRNA in different lymphoid tissues may play an important role in regional immunoregulation.
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PMID:Tissue-specific regulation of IL-4 mRNA expression in human tonsil. 750 59

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

The in vitro effect of single or combined doses of zidovudine (AZT) and dideoxycytidine (ddC) on the production and utilization of interleukin-2 (IL-2) by normal human peripheral blood mononuclear cells (PBMC) was evaluated by measuring IL-2 concentrations in supernatants from PHA-stimulated PBMC cultures. Drugs were added at the beginning of the culture period and left throughout. Whereas AZT alone (1 and 10 microM) caused only a slight increase, ddC alone (1 and 10 microM) and combined AZT/ddC (1 + 1 and 10 + 10 microM) caused a considerable increase. IL-2 gene expression in the drug-treated PBMC did not increase. This finding suggested that the increased supernatant IL-2 accumulations might be caused by a drug-induced down-regulation of the IL-2 receptor alpha (IL-2R alpha, CD25). AZT decreased IL-2R alpha expression, but only slightly. In contrast, ddC alone and combined AZT/ddC decreased the CD25 molecules in a marked and dose-dependent manner. They also markedly reduced IL-2R alpha gene expression. These findings show that the dideoxynucleoside drugs tested left PHA-induced IL-2 gene activation unchanged but decreased IL-2R alpha gene activation, thus down-regulating IL-2R alpha cell-surface protein expression.
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PMID:Down-regulation of interleukin-2 receptor gene activation and protein expression by dideoxynucleoside analogs. 760


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