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)

The induction of HLA class II antigens on graft tubular cells and IL-2 receptor expression on the infiltrating lymphoid cells was studied in 245 prospective aspiration biopsies taken during the first posttransplant month from 20 human renal allografts with histologically verified acute vascular rejection (AVR). Based on the histological findings, the specimens were categorized into two main groups: biopsies from grafts with features of AVR only, and biopsies with a combination of AVR and acute cellular rejection (ACR). Also in the second group the AVR findings were predominant. Biopsies were further divided into two subgroups, depending on whether the rejection was reversible or irreversible. Evaluation of class II and IL-2R expression was done by indirect immunoperoxidase staining using monoclonal antibodies. The initial posttransplant tubular cell class II expression was low in all 20 grafts, with 5-15% positive tubular cells, and IL-2R expression was negative. All 13 grafts with a combination of AVR and ACR displayed class II induction, closely correlating to the blast response, with 50% positive tubular cells on days 2-7 after the onset of rejection, and declining thereafter back to prerejection level in grafts with reversible rejection. In grafts with irreversible rejection, tubular cell class II expression remained elevated. A similar pattern was observed with regard to IL-2R expression: the IL-2R positive cells disappeared from the grafts with reversible rejection, but they persisted in the irreversible rejections. The same pattern of class II and IL-2R expression was observed in grafts with pure AVR and reversible rejection. Instead, completely different findings were seen in grafts with pure AVR and irreversible rejection: there was neither class II induction on tubular cells nor IL-2R expression on lymphoid cells. The persistant inflammation was dominated by mononuclear phagocytes, and no blast response could be detected during the entire follow-up. These findings demonstrate a close relationship between IL-2R expression and tubular cell class II induction also in AVR, in the majority of cases. On the other hand, the findings in grafts with pure AVR in histology and irreversible rejection suggest that AVR is a heterogenous group of rejections, where different cellular and molecular mechanisms are operating.
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PMID:Induction of HLA class II antigen and interleukin 2 receptor expression in acute vascular rejection of human kidney allografts. 158 71

The proliferative response of peripheral blood mononuclear cells (PBMC) in synthetic serum-free media depends on the presence of sufficient amounts of transferrin (Tf). In the present communication we show that the reduction of Tf concentration in culture media results in a decreased proliferation, whereas lymphokine production and the expression of activation markers (IL-2 receptor; transferrin receptor, (TfR); HLA class II) remain unchanged. To examine whether this effect is due to iron depletion we added iron chelates (ferric citrate, FeCi; ferric nitrilotriacetic acid, FeNTA) which can be internalized by cells without the requirement for Tf. The iron chelates could fully restore the proliferative response even in complete absence of Tf, suggesting that the observed inhibitory effect was indeed caused by iron depletion. Addition of a monoclonal TfR antibody, J 64, also caused a marked inhibition of proliferation of PBMC in regular serum-containing medium as well as in Tf-free synthetic medium; this effect could not be overcome by any of the tested iron chelates. Therefore, growth inhibition caused by J 64 cannot simply be attributed to iron starvation. These data suggest that J 64 may interfere with processes others than iron uptake and that the TfR might confer a necessary promoting signal for lymphocyte proliferation.
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PMID:The role of the transferrin receptor for the activation of human lymphocytes. 198 60

The presence of IL-2 receptor and HLA class II antigens as detected by monoclonal antibodies on mononuclear cells from both cerebro-spinal fluid (CSF) and peripheral blood was examined by cytofluorographic analysis in patients with multiple sclerosis (MS) and other neurological diseases. CSF as compared to blood was enriched in cells expressing IL-2 receptor and HLA class II molecules both in MS patients and in other inflammatory diseases of the central nervous system suggesting that activated T-cells concentrate within the central nervous system.
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PMID:IL-2 receptor and HLA class II antigens on cerebrospinal fluid cells of patients with multiple sclerosis and other neurological diseases. 303 41

In Type I diabetes the observation of a decreased release of interleukin-2 (IL-2) and soluble IL-2 receptors by means of stimulated lymphocytes in vitro indicates that a primary immunoregulatory defect may be involved. To confirm this hypothesis we investigated the T-cell activation trend, evaluating the surface expression of IL-2 receptor (CD25), transferrin (CD71), HLA class II (DR), and CD69 phenotypes after in vitro stimulation with phytohemagglutinin (PHA; 1 and 10 micrograms/ml) and concanavalin A (12.5 micrograms/ml) in six newly diagnosed Type I diabetics and six islet cell- and insulin autoantibody-positive first-degree relatives. As controls were studied six long-standing Type I diabetics and six healthy subjects. T-cell cultures from the four groups were performed on the same day and examined at 0, 24, 48, 96, 120, and 144 hr. Cytometric analysis was performed, keeping PBMC gating constant on the basis of physical parameters (scatter and volume). Using both PHA concentrations, a lower level of CD25, CD71, CD69, and DR antigen expression was found in newly diagnosed patients at all observation times with respect to control cultures (P < 0.001). Unexpectedly, pre-Type I diabetic subjects, after 1 microgram/ml of PHA, showed a significantly reduced expression of CD69 (P < 0.001) and CD71 (P < 0.001). The levels remained low, also with high PHA, at the different observation periods, while CD25 expression was found to be reduced in prediabetics only after 1 micrograms/ml of PHA (P < 0.001). The long-standing patients showed a T cell activation trend very close to the latter. Our data show that in Type I diabetes and in the early phases of the disease, the initial activation signal(s) appears to be affected, particularly with one or more subsequent events necessary to initiate the appearance of "activation antigens." This study suggests that the natural history of immunoregulation in pre-Type I and Type I diabetes is characterized by a primary defect in this system, which also persists in patients with long-standing disease.
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PMID:Study of T-cell activation in type I diabetic patients and pre-type I diabetic subjects by cytometric analysis: antigen expression defect in vitro. 809 71

Superantigen-mediated T cell activation requires the participation of antigen-presenting cells (APC). Once superantigen has bound class II MHC molecules on the surface of APC, it then can interact with the T cell receptor to induce T cell activation. Superantigen-mediated T lymphocyte activation, along with its consequent cytokine production is thought to be the basis for the pathophysiology of conditions such as toxic shock syndrome, Kawasaki's disease and possibly rheumatoid arthritis. We examined the role of CD56+ NK lymphocytes in the interaction between superantigens and T lymphocytes. First, we found that a subpopulation of CD56+ cells freshly isolated from human peripheral blood expressed class II MHC molecules. The amount of HLA-DR expression varied between individuals, ranging from 9.3% to 37.7%. CD56+ (NK) cells were purified from the peripheral blood by cell sorting and were tested for their ability to support SEB-mediated T cell activation as assessed by surface expression of IL-2 receptor alpha-chain (CD25) on CD3+ lymphocytes. We observed that when enriched T cells were incubated with SEB in the presence of NK cells, there was a significant up-regulation of CD25 expression of the T cells. When HLA-DR+ cells were removed from sorted CD56+ populations, the remaining HLA-DR- NK cells were unable to support SEB-mediated T cell activation. Also, SEB up-regulated the expression of HLA-DR on CD56+ cells in peripheral blood mononuclear cell (PBMC) populations after 24 h of incubation, implying that the ability of NK cells to function as superantigen-presenting cells is up-regulated by superantigens themselves. Together, these data demonstrate for the first time that human CD56+ HLA-DR+ NK cells can function as superantigen-presenting cells, and imply that NK cells may be involved in the activation of non-specific T cell reactivity during early host defences against superantigen-elaborating microorganisms in vivo. Furthermore, the physical linkage of NK cells and T cells by the interaction of superantigen with HLA class II molecules and T cell receptors, respectively, may lead to NK cell activation and augmented lytic potential, helping to clear the body of superantigen-elaborating microorganisms.
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PMID:Human natural killer (NK) cells present staphylococcal enterotoxin B (SEB) to T lymphocytes. 862 34

Lymphocyte activation gene (LAG)-3, a member of the Ig superfamily, has been characterized as an activation antigen of T cells and NK cells. LAG-3 has been proposed as an alternate ligand for HLA class II due to some sequence homology and similarities in exon-intron organization with CD4. Here, we report the functional evaluation of a soluble Ig fusion molecule of human LAG-3 (LAG-3-Ig) in T cell activation assays. Cytofluorimetry studies revealed LAG-3-Ig binding predominantly to class II-expressing cells. In functional assays, inhibition of primary allogeneic mixed lymphocyte response (MLR) and murine-human xenogeneic MLR was observed in the presence of LAG-3-Ig. Effects of LAG-3-Ig addition were not observed on mitogen-, recall antigen- or superantigen-mediated stimulation. Cytotoxic T lymphocyte effector functions were also not affected by LAG-3-Ig. Inhibition of alloresponses by LAG-3-Ig occurred within the first 24 h of activation, resulting in a strong inhibition of IL-2 production. Unlike blockade of the CD28 receptor, however, LAG-3-Ig-mediated inhibition could not be reversed by exogenous IL-2 supplementation. Cytofluorimetric analysis of the phenotype of cells exposed to LAG-3-Ig in MLR cultures revealed a decrease in IL-2 receptor expression (CD25) on CD4+ cells in all donors tested. Based on the results from these studies, we conclude that LAG-3-Ig inhibits alloresponses of naive peripheral blood lymphocytes, by blocking the activation of a subpopulation of allo reactive cells.
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PMID:Soluble human lymphocyte activation gene-3 modulates allospecific T cell responses. 964 16

We studied the effect of protein-bound polysaccharide PSK on the activation of the human natural killer cell line NKL. We observed an increased natural killer cytotoxic activity against different tumor cells (K562, Daudi, and U937) when a standard 2- to 3-h 51chromium release assay was performed. The results parallel those obtained after treatment of the NKL cell line with interleukin-2. The highest cytotoxic activity was reached at a concentration of 100 microg/ml of PSK. This natural killer activation was inhibited when the PSK dose was 1,000 microg/ml. None of the cell surface markers that were analyzed by fluorescence-activated cell sorting showed variations after PSK or interleukin-2 treatment of NKL cells. These markers included CD2, CD11b, CD11c, CD18, CD16, CD54, CD56, CD98, CD25, CD122, HLA class I, HLA class II, CD94, ILT2, p58.1, p70, and NKp46. One of these markers (NKp46) is a major triggering receptor reported to be involved in the natural cytotoxicity of fresh or cultured human natural killer cells. In our study, another triggering receptor must be implicated in PSK-induced natural killer lysis. Our data suggest that PSK is an important biological response modifier of natural killer cells in vitro and may prove to be useful for the study of human natural killer cell biology.
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PMID:Protein-bound polysaccharide (PSK) induces cytotoxic activity in the NKL human natural killer cell line. 1078 73

Graft rejections as well as tolerance are true representation of the specificity, sophistication and redundancy of an elegantly and meticulously designed immune system. Tolerance is in a way similar to the process of self-recognition where lymphoid clones, during development, baring self-reactive receptor are eliminated or rendered in active by "clonal deletion" leading to a state of accommodation and acceptance (anergic). On the other hand, both acute and chronic rejections are manifestation of the purpose of existence of the immune system, which is to defend the host against foreign invaders. Thus, in order to treat (control) graft rejection it is necessary to determine and understand the steps leading to recognition, stimulation, activation, and amplification of the immune system. The first step leading to the initiation of the immune system cascade is recognition. Which can either be direct where donor antigens of the major histocompatibility complex (MHC) expressed on the donor cells (passenger leukocytes) or tissues are recognised by the host immune system. The direct recognition pathway initiates acute graft rejection. Alternatively processed donor MHC peptides presented by the recipient antigen presenting cells (APC) initiate the indirect pathway of immune response, which is as important as the direct recognition especially in chronic rejection. Recognition is followed by the ligation of a series of adhesion molecules starting with an antigen to its specific T-cell receptor (TCR)/cluster of differentiation (CD) complex, expressed on the surface of the T cell. In order for the activation to precede additional costimulatory signals, such as ligation of the CD28/B7, CD4/HLA class II and CD/HLA class I antigens are required. The activation process is accompanied by an increase of cytokines production such as interleukin (IL)-2, IL-12, interferon (INF) and tumour necrosis factor (TNF) by the primed T cell. The complexity and the polymorphic nature of the immune system have necessitated designing agents that inhibit the immune system at different levels. Cyclosporine and Tacrolimus, collectively known as calcineurin inhibitors, seems to act on the IL-2 by inhibiting its production thus leading to a decrease in the proliferation of the activated lymphocyte. Rapamycin, which is similar to Tacrolimus, inhibits graft rejection by blocking IL-2 activation and phosphorylation of 70 S6 kinase thus inhibiting the progression of T-cell from G to S phase. While Cellcept (MMF) reduce the proliferation of T cell by inhibiting purine synthesis and by its action on ionosine monophosphate dehydrogenase. Anti-lymphocyte antibodies (ATG) deplete circulating lymphocytes while selective monoclonal antibodies are directed against IL-2 receptor thus reducing the rate of proliferation of activated T cells. Recently, antibodies to the CD40/CD40 ligand have been shown to induce long-term graft survival with the inhibition of the Th1 cytokines (INF), IL-2 and IL-12 and upregulating the Th2 cytokines IL-4 and IL-10. Lastly graft rejection can be reduced by blockade of the B7/CD28 costimulation pathway with the fusion protein CTLA-4Ig. With the availability of such potent and diverse agents it is now possible to develop multi drug regiments that can depress the immune system at the different steps of the activation cascade, with minimal side effects, thus improving graft and patient survival rates.
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PMID:The mosaic of immunosuppressive drugs. 1283 79