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)

Natural suppressor cells exhibiting a double-negative, immature T cell phenotype have been identified in maternal spleen during syngeneic murine pregnancy. In the present study, splenic pregnancy-associated natural suppressor (SPANS) cells are shown to express alpha/beta T cell receptors. SPANS cell-mediated inhibition of DNA synthesis by spleen cells responding in mixed lymphocyte reactions (MLR) is associated with a reduction in interleukin (IL)-2 bioactivity beginning after 96 h of culture. Although culture supernatants from suppressed MLR exhibit diminished ability to support the growth of IL-2-dependent CTLL-2 cells, SPANS cells themselves are unable to inhibit IL-2-driven CTLL-2 proliferation, suggesting that SPANS cells down-regulate IL-2 synthesis in MLR. IL-2 utilization in MLR is also inhibited by SPANS cells, since the addition of exogenous IL-2 fails to relieve the inhibitory effect of SPANS cells on lymphoproliferative responses in MLR. Flow cytofluorometric analysis reveals that MLR performed in the presence of SPANS cells contain normal percentages of CD4 and IL-2 receptor-bearing spleen cells. Thus, SPANS cells do not inhibit cellular proliferation in MLR by selectively interfering with clonal expansion of IL-2-producing helper T cells or by down-regulating IL-2 receptor expression. We have determined that SPANS cells inhibit DNA synthesis in MLR via the production of a transforming growth factor (TGF)-beta 1-like suppressor factor, since cellular proliferation in MLR is restored to normal levels in the presence of anti-TGF-beta 1 neutralizing antibody. However, IL-2 bioactivity in these cultures remains low in comparison to control MLR, suggesting the presence of a second distinct suppressor factor. Although the identity of this second inhibitory molecule has yet to be determined, neutralizing antibody studies have ruled out IL-10.
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PMID:Inhibition of DNA synthesis and IL-2 bioactivity in MLR by splenic pregnancy-associated natural suppressor cells involves the production of a TGF-beta 1-like molecule and a second distinct inhibitory factor. 827 Dec 38

Human interleukin 2 (IL-2) is a member of the class of crucial regulators of lymphocyte proliferation. The action of IL-2 is known to be mediated through binding to a specific IL-2 receptor (IL-2R) which comprises at least two distinct proteins: IL-2R alpha (p55) and IL-2R beta (p70-75). However, the expression and function of IL-2R are largely unknown in acute myeloblastic leukemia cells. In a human granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or stem cell factor-dependent myeloid leukemia cell line (M07E), IL-2 was found to stimulate proliferation in a dose-dependent manner and to augment GM-CSF- and stem cell factor-induced proliferation of M07E cells. The expression of IL-2R beta on M07E cells was detectable with 125I-IL-2 binding and affinity cross-linking analyses and with a monoclonal antibody against IL-2R beta, Mik-beta 1. Although the expression of IL-2R beta was not down-regulated but somewhat up-regulated by treatment with GM-CSF in both mRNA and protein levels, GM-CSF was found to compete (75%) with radiolabeled IL-2 for binding to IL-2R on M07E cells, whereas no competition of GM-CSF binding was observed with IL-2 even at a 400-fold molar excess. These results suggest that IL-2R may be functionally expressed in some cases of acute myeloblastic leukemia cells and raise the possibility that IL-2 may have some effects on human myelopoiesis.
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PMID:Functional expression of interleukin 2 receptor in a human factor-dependent megakaryoblastic leukemia cell line: evidence that granulocyte-macrophage colony-stimulating factor inhibits interleukin 2 binding to its receptor. 842 2

The very late antigens, VLA-4 and VLA-5 belong to the beta 1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+CD4-CD8- gamma delta TCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low gamma delta T cells specifically adhere to FN. The binding capacity is inhibited by the synthetic peptide GRGDSP which inhibits adhesion mediated by VLA-5 and a functional mAb directed against the alpha 4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting gamma delta T cells cultured on coimmobilized anti-TCR delta 1 mAb and FN or the 40 kDa fragment (which contains the adhesion site in the IIICS domain recognized by VLA-4) for 96 h in the absence of exogeneous IL-2 showed significant increase in proliferation when compared to that of resting gamma delta T cells cultured on immobilized anti-TCR delta 1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCR delta 1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting gamma delta T cells induced by cross-linked TCR delta 1. These results suggest that the gamma delta T cell beta 1 integrins, VLA-4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules.
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PMID:Adhesion and costimulation of proliferative responses of human gamma delta T cells by interaction of VLA-4 and VLA-5 with fibronectin. 850 48

An interleukin (IL)-4 dependent mouse T cell clone 8.2 derived from an IL-2-dependent T cell line was characterized. As measured by flow cytometric analysis and Northern blotting, it expresses IL-2 receptor beta (IL-2R beta) and gamma (IL-2R gamma) chains, but has lost expression of IL-2 receptor alpha chain (IL-2R alpha). To investigate the properties of the mouse IL-2R beta gamma complex and the role of IL-2R alpha gene expression, this clone was further studied. T cell clone 8.2 has lost the capacity to bind 125I-labeled human IL-2 under experimental conditions able to detect intermediate-affinity IL-2R in human cells. Mouse IL-2 is unable to block the binding of mAb TM beta 1 to 8.2 cells. Under the same experimental conditions, mouse IL-2 blocks the binding of TM beta 1 to C30-1 cells expressing the IL-2 alpha beta gamma complex. Since TM beta 1 recognizes an epitope related to the IL-2 binding site of IL-2R beta, these results can be taken as a demonstration that mouse IL-2R beta gamma does not bind mouse IL-2. Furthermore, T cell clone 8.2 does not proliferate in response to recombinant mouse or human IL-2. On the other hand, T cell transfectant lines expressing heterospecific receptors made of the human IL-2R beta and mouse IL-2R gamma chains bind 125I-labeled human IL-2 and proliferate in response to IL-2. This establishes the difference between mouse and human IL-2R beta chains. Transfection of T cell clone 8.2 with human IL-2R alpha genes restores their capacity to proliferate in response to IL-2. In addition, all transfectants grown in IL-2 express the endogeneous mouse IL-2R alpha chain. When grown in IL-4, the endogeneous mouse IL-2R alpha gene remains silent in all these transfectants. These results show that, contrary to the human, the mouse does not express an intermediate-affinity IL-2R. Expression of the IL-2R alpha gene is therefore required for the formation of the functional IL-2R in mice.
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PMID:Lack of intermediate-affinity interleukin-2 receptor in mice leads to dependence on interleukin-2 receptor alpha, beta and gamma chain expression for T cell growth. 856 67

Studies from our laboratory indicate that n-3 (fish oil, FO) lipids at 10% (w/w) in a nutritionally adequate, semipurified diet, and supplemented with equal levels of antioxidants, extended the life span of lupus-prone (NZB/NZW)F1 (B/W) female mice as compared to n-6 (corn oil, CO) lipids. The early rise of autoimmune disease in CO-fed mice was closely linked to the loss of T-cell function. Both IL-2 production and IL-2 receptor expression were reduced due to the loss of naive T-cells and a rise in memory T-cells. Proliferative response to both mitogens and superantigens (staphylococcal enterotoxins A and B) was higher in FO-fed 6.5-mon-old mice. These changes paralleled decreased PGE2 production by splenic cells from FO-fed mice. Analysis of mRNA expression in different organs revealed differential effects of dietary lipids. In FO-fed mice, transforming growth factor beta 1 (TGF beta 1) expression was decreased in kidneys, but splenic tissues had higher expression of TGF beta mRNA. As TGF beta promotes programmed cell death (PCD), we studied the effects of CO and FO on PCD rates in lymphocytes. Both propidium iodide staining and DNA fragmentation were elevated in lymphocytes of FO-fed mice when compared to CO-fed mice of similar age. Also, increased PCD correlated closely with increased Fas gene expression. Thus, in addition to various other antiinflammatory effects, dietary FO appears to increase PCD and prevent accumulation of self-reactive immune cells in lymphoid organs. Further studies are required to dissect the pro- and antiinflammatory mechanisms associated with dietary n-3 and n-6 lipids in modulating autoimmune disorders or malignancy during aging.
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PMID:Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. 872 1

The regulation of human natural killer (NK) cell activation is under the control of a network of regulatory signals provided by cytokines. In the present study, we investigated the functional interaction between interleukin (IL)-4 and two monocyte/macrophage-derived cytokines, IL-12 and IL-15, during the process of NK stimulation. Using freshly isolated human NK cells, we have demonstrated that IL-4 negatively regulates lymphokine-activated killer (LAK) activity induced by IL-15 against the NK-resistant Daudi target cells. In contrast, IL-4 had no effect on IL-12-stimulated LAK generation. The differential effect of IL-4 on NK cell activation by IL-12 and IL-15 correlates with its ability to increase or to down-regulate the level of tumor necrosis factor-alpha and interferon-gamma release by NK cells, respectively. In contrast, endogenous transforming growth factor-beta 1 does not appear to be involved in the IL-4 regulatory pathway. Furthermore, while IL-4 was found to decrease the basal expression of the IL-2 receptor beta subunit utilized by IL-15, it had no effect on the expression of the beta 1 chain of the IL-12 receptor compared to untreated cells. Northern blot analysis indicated that the IL-4 regulatory effect on NK lytic function was associated with its capacity to down-regulate granzyme B and perforin gene transcription in response to IL-15 and its failure to affect the expression of both gene's in response to IL-12. Together, these data suggest the existence of a distinct cross-talk between IL-4 and IL-15 or IL-12 signaling pathways during the regulation of human non-major histocompatibility complex-restricted cytotoxicity.
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PMID:Differential regulation of interleukin-12- and interleukin-15-induced natural killer cell activation by interleukin-4. 892 63

We recently identified a CD2-mediated, IL-12-dependent signaling pathway that inhibits apoptosis in mitogen-stimulated human gammadelta-T cells. Here we show that gammadelta-T cells which acquire resistance to mitogen-induced apoptosis upregulate IL-12 receptor beta 1 subunit (IL-12Rbeta1); in contrast, gammadelta-T cells which remain sensitive to mitogen-induced apoptosis fail to express IL-12Rbeta1. Next we show that gammadelta-T cells which are rendered resistant to mitogen-induced apoptosis attenuate their expression of the IL-2 receptor alpha chain (IL-2Ralpha/CD25), this in part accounting for their acquired resistance to IL-2-induced death. In contrast, apoptosis-sensitive gammadelta-T cells are shown to persist in their expression of IL-2Ralpha/CD25, thus remaining sensitive to IL-2-induced death. Moreover, we show that apoptosis-resistant, but not apoptosis-sensitive, gammadelta-T cells display an enhanced responsiveness to IL-15, a finding in keeping with the known function of IL-15 as a growth and survival factor. Finally, we present evidence to suggest that this differential responsiveness to IL-15 occurs in part by the increased expression of the IL-15Ralpha chain on apoptosis-resistant gammadelta-T cells, compared to apoptosis-sensitive gammadelta-T cells. The biological and clinical implications of these findings are discussed.
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PMID:Down-regulation of IL-2 receptor alpha (CD25) characterizes human gammadelta-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12. 1180 26


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