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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 130-base pair fragment located between 220 and 90 base pairs upstream of the major transcription initiation site of the human interleukin 2 (IL-2) receptor gene had positive regulatory effect on the early promoter of simian virus 40 as well as its own promoter. This fragment seems to be responsible for not only cell-specific but also lymphokine-induced expression of the IL-2 receptor gene as assessed by DNA transfection. The same DNA fragment directed cell-specific transcription of the IL-2 receptor gene in extract of HTLV-I-infected T cells, MT-1, but not of Epstein-Barr virus-transformed B cells, CESS. The addition of small amounts of MT-1 extract to CESS extract resulted in specific expression of the IL-2 receptor gene, indicating that cell-specific expression is regulated by trans-acting molecules in MT-1 extract.
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PMID:The human IL-2 receptor gene contains a positive regulatory element that functions in cultured cells and cell-free extracts. 303 Oct 40

Interleukin-2 (IL-2) in combination with the IL-2 receptor has an essential role in antigen-stimulated proliferation of T lymphocytes. It has been proposed that the constitutive expression of the IL-2 receptor on adult T-cell leukaemia (ATL) cells may be associated with transformation of T cells. Although we and others have isolated complementary DNA clones encoding a protein that binds IL-2, formal proof that this protein is the IL-2 receptor requires demonstration of IL-2-dependent growth stimulation of cells expressing the protein. In addition, a functional assay system other than binding of IL-2 is required to investigate the molecular mechanism of signal transmission through the IL-2 receptor using artificially mutated cDNA. The IL-2 receptor expressed in non-lymphoid cells by cDNA transfection did not mediate a growth signal, implying that lymphoid cells expressing the functional receptor might have specific accessory molecule(s) for signal transmission by the receptor. Therefore, we established a line of IL-2-dependent mouse cells (CT/hR) expressing both murine (endogenous) and human IL-2 receptors. Here, by blocking the endogenous mouse IL-2 receptors with monoclonal antibodies, we show that the human IL-2 receptor of CT/hR cells is functionally active. Although CT/hR expressed the human IL-2 receptor constitutively, growth of these cells was strictly dependent on IL-2, indicating that uncontrolled over-expression of the IL-2 receptor was not by itself sufficient for T-cell transformation.
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PMID:Expression of functional human interleukin-2 receptor in mouse T cells by cDNA transfection. 308 15

The establishment of IL-2-independent T-cell lines spontaneously derived from long-term IL-2-dependent cytotoxic T-cell lines is described. Two lines (cloned and uncloned) studied in detail have shown the following characteristics: (1) Permanent loss of IL-2 dependence. (2) Partial or complete loss of both cytotoxic activity and the IL-2 receptor. (3) Increased expression of T-cell membrane markers (Thy1.2, Lyt1.2) compared with the parental line. (4) Lower level of DNA methylation than in freshly obtained lymphoid cells. (5) Different karyotypic pattern from the parental IL-2-dependent line, with a mean number of 39-40 chromosomes and a resemblance to T leukemic lines. (6) Leukemia caused in normal syngeneic C57BL/6 mice by the uncloned line, in contrast to the cloned IL-2-independent line or the parental dependent line. Unlike established leukemic lines, however, the independent line gave rise to tumors which regressed in some mice within a few days of their appearance. These findings suggest that T-cell lines maintained with IL-2 for prolonged periods of time (greater than 3 months) can undergo transformation and, therefore, should not be utilized for immunotherapeutic purposes.
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PMID:Characterization of a tumorigenic murine T-lymphoid-cell line spontaneously derived from an IL-2-dependent T-cell line. 308 91

MRL/MP-lpr/lpr (MRL/l) mice spontaneously develop an age-related autoimmune disease concomitant with interleukin-2 (IL-2) defects. Induction of IL-2 receptor (IL-2R), IL-2 production and subsequent de novo DNA synthesis in MRL/l mice by the tumour-promoting phorbol ester 12-o-tetradecanoyl phorbol 13-acetate (TPA) and calcium ionophore (A23187) were examined. These two compounds given together induced significant IL-2R expression, IL-2 production, and de novo DNA synthesis of spleen cells from this murine strain, as did concanavalin A (Con A) plus TPA. TPA and A23187 may bypass the early steps of activation by mitogens in murine lymphocytes. However, even though these IL-2 defects could be overcome to some extent, the response of MRL/l mice to these stimuli was considerably lower than the enhanced IL-2R expression and IL-2 production of MRL/MP-+/+(MRL/n) control mice. These results suggested that the failure to respond to mitogens in these mice may be due, at least in part, to failure of receptor signal transduction, and to defects of molecular and biochemical reactions following signal transduction.
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PMID:Synergistic induction by calcium ionophore and phorbol ester of interleukin-2 (IL-2) receptor expression, IL-2 production, and proliferation in autoimmune MRL/MP-lpr mice. 309 71

Interleukin-2 (IL-2) for a long time has been considered as a T-cell specific growth factor which acts through distinct surface receptors present on activated, but not on resting, T-lymphocytes. Recently it has been shown that activated murine and human B-cells also express IL-2 receptors and respond to IL-2 with an increase of DNA synthesis. Some human B-cell malignancies have been reported to react with anti-IL-2 receptor antibodies, but no response to IL-2 has been documented in these cases. Here, in five of 11 B-cell leukemia/lymphoma cases, we identified cells which not only express the IL-2 receptor, but also respond to IL-2 stimulation, as shown by a marked increase of 3H-thymidine incorporation and by differentiation of lymphoma cells. The IL-2-induced 3H-thymidine uptake was completely blocked by a monoclonal antibody to IL-2 receptor, which indicates that IL-2 acted directly through functional IL-2 receptors.
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PMID:Malignant B-cells have receptors for and respond to interleukin-2. 310 Aug 85

Monocyte-depleted human T lymphocytes completed a single round of DNA synthesis and cell division when treated with phytohaemagglutinin (PHA). Direct assay of culture supernatants showed that very low amounts of interleukin-2 (IL-2) were synthesized in these cultures. Furthermore, the first round of cell division was totally unaffected by the addition of saturating amounts of anti-Tac, a monoclonal antibody against the IL-2 receptor. These data strongly suggest that stimulation of IL-2 receptors by IL-2 was not required for the completion of the first round of mitosis. By contrast, proliferation of the daughter cells produced by the first cell doubling required the addition of exogenous IL-2 and was totally abolished by anti-Tac. These results were confirmed by experiments using single lymphocytes, which also showed that accessory cells were not required during the first cell doubling of PHA-stimulated lymphocytes. We therefore propose a modified model for in vitro T-lymphocyte activation, wherein PHA stimulate a single round of cell proliferation without a requirement for stimulation by IL-2. The resulting daughter cells now require IL-2 for further proliferation. By analogy, we suggest that triggering by antigen in vivo (in the context of products of the major histocompatibility locus) may also stimulate a single round of IL-2-independent division in appropriate clones of T lymphocytes, with the resulting population of daughter cells requiring IL-2 for further expansion of the population.
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PMID:Human T lymphocytes stimulated by phytohaemagglutinin undergo a single round of cell division without a requirement for interleukin-2 or accessory cells. 310 52

Expression of the activation-associated 4F2 antigen, transferrin receptor and interleukin-2 (IL-2) receptor on suspended cells from 75 biopsied low-grade non-Hodgkin lymphomas (L-NHL) of B-cell origin was correlated to patient survival, clinical prognostic parameters and estimated DNA synthesis. 4F2 antigen expression correlated significantly with poor patient survival, high DNA synthesis and transferrin receptor expression. Transferrin receptor expression was associated with high DNA synthesis and treatment response, but not with patient survival. On the other hand, IL-2 receptor was correlated neither to patient survival nor to other studied markers for cell activation, but seemed to be expressed on certain subsets of lymphomas. We suggest that monoclonal antibody (MAb) against the activation-associated 4F2 antigen could be used to select patients with L-NHL for aggressive chemotherapy.
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PMID:The activation-associated antigen 4F2 predicts patient survival in low-grade B-cell lymphomas. 310 47

Monoclonal antibody 60.3 defines the leucocyte antigen CD 18 and recognizes a cell surface glycoprotein with an apparent molecular weight (MW) of 90,000 expressed by most human peripheral blood and bone marrow cells. This antibody can, among other things, block phorbol ester-induced adhesion among human mononuclear leucocytes. We show in this study that phorbol esters alone can induce peripheral blood mononuclear cells (PBL) to secrete interleukin-2 (IL-2) and that the IL-2-dependent cell line CTLL can be used for measuring this lymphokine without influence of the phorbol esters themselves. These findings make it possible to analyse the capacity of antibody 60.3 to interfere with IL-2 production and receptor expression by phorbol ester or phytohaemagglutinin (PHA)-treated human PBL. A significant positive correlation between blockage of induced cell aggregation by antibody 60.3 and reduction in IL-2 release was observed. The addition of interleukin-1 (IL-1) restored IL-2 secretion in PHA-treated, but not in 4-beta-phorbol 12, 13-dibutyrate [P(Bu)2]-treated, cells in the presence of this antibody. In parallel, IL-2 receptor expression was determined by immunofluorescence using biotinylated anti-IL-2 receptor (Tac) antibodies. FACS analysis showed that IL-2 receptor expression was unaffected by antibody 60.3, whereas DNA synthesis of the same P(Bu)2-treated PBL was inhibited. However, addition of external recombinant IL-2 overcame this proliferation blockade. These results indicate that a cell-to-cell adhesion step is necessary for the production of IL-2, but not for the expression of its receptor on both PHA- and P(Bu)2-treated human PBL.
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PMID:A monoclonal antibody inhibiting leucocyte adhesion blocks induction of IL-2 production but not IL-2 receptor expression. 310 39

Human r-DNA IL-2 and fluorescent (Fl) mouse anti-human IL-2 receptor antibody have been tested separately and in competition with each other for their capacities to bind to the splenocytes of Xenopus laevis, the South African clawed toad. Binding by Fl*-mouse anti-DNP antibody of the same subclass (IgG1, kappa) was used as a control. The results of visual tests using rIL-2 coated fluorescent Covaspheres demonstrate that the human mediator will bind cells of the toad spleen. Moreover, the mediator inhibits binding of the antibody against the human IL-2 receptor, as detected by cytofluorimetry. Some of the IL-2 receptors on the toad cells appear to be constitutive, since they are expressed on freshly biopsied lymphocytes. Activation of these cells in vitro will increase the percentage of those cells able to bind both the anti-receptor antibody and rIL-2. Since the human mediator is only able to modulate in vivo immune activity in antigen-activated toads, it appears that in spite of having some constitutive IL-2 receptors, a quantitative increase in receptor expression is required before immunological behavior can be effected. More stringent controls of receptor expression may have provided an additional regulatory level as mammalian mechanisms evolved.
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PMID:Toad splenocytes bind human IL-2 and anti-human IL-2 receptor antibody specifically. 310 43

Although activated human T and B lymphocytes express both high-affinity and low-affinity membrane receptors for interleukin-2 (IL-2), the structural features that distinguish these receptors have remained unresolved. The high-affinity receptors appear to mediate IL-2 induced T cell growth and internalization of IL-2, whereas no function has yet been ascribed to the low-affinity receptors. The Tac antigen is an IL-2 binding protein of relative molecular mass 55,000 (Mr 55K) that participates in the formation of both high- and low-affinity receptors. But Tac complementary DNA transfection and membrane fusion studies have suggested that additional T-cell components are required to produce high-affinity IL-2 receptors. In this study, we report the identification of a second human IL-2 binding protein that (1) has an Mr of approximately 70K, (2) lacks reactivity with the anti-Tac antibody, (3) binds IL-2 with intermediate affinity and (4) is present on the surface of resting T cells, large granular lymphocytes (natural killer cells), and certain T and B cell lines in the absence of the Tac antigen. Chemical crosslinking of 125I-labelled IL-2 bound to high-affinity IL-2 receptors produces labelling of both the p70 protein and the Tac antigen and the anti-Tac antibody blocks the crosslink detection of both of these proteins. Expression of Tac cDNA in a T cell line expressing the p70 protein, but lacking both Tac and high-affinity receptors, results in the reconstitution of high-affinity IL-2 receptors in these cells. Together, these findings suggest that the high-affinity human IL-2 receptor may be a membrane complex composed of at least the p70 protein and Tac antigen.
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PMID:A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. 310 74


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