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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 2(IL-2) is known to stimulate the progression of activated T cells from G1 through the rest of the cell cycle. We have demonstrated that addition of purified recombinant human IL-2 (rIL-2) to fresh normal human peripheral blood mononuclear cells (PBM), which were IL-2 receptor (Tac) negative by FACS analysis, stimulated marked proliferation of the PBM. IL-2-induced proliferation was also observed with umbilical cord blood mononuclear cells. Monocyte depletion of PBM resulted in a marked reduction of rIL-2-induced proliferative response which could be restored by adding back autologous irradiated monocytes but not by interleukin 1. The T cells preincubated with rIL-2 showed a five to six times enhanced autologous mixed-lymphocyte reaction (AMLR) compared to controls. The rIL-2-induced proliferative response of PBM was inhibited in a concentration-dependent fashion by preincubation of PBM with an anti-HLA-DR framework monoclonal antibody. The proliferating cells were shown by two-color flow cytometric analysis to be primarily Leu-1+ and Leu-4+ T cells (both leu-3+ and Leu-2+ subsets); however, 6 to 19% of responding cells had surface markers for B cells or NK cells. The data demonstrate that rIL-2 can induce proliferation of "resting" human T cells. The phenomenon may be related to a monocyte-dependent AMLR which induces IL-2 receptors and IL-2 responsiveness in a subset of T cells.
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PMID:Interleukin 2 induces proliferation of normal "resting" human T cells in the absence of other known external stimulation. 295 83

Interleukin 2 (IL-2) functions in the regulation of cell-mediated immune responses both in vivo and in vitro. Therefore, IL-2 production has been studied in patients with immunological disorders to determine the level of the immune defect. However, the cause(s) of low responses to selected antigens by cells from clinically normal individuals has not been examined. The ability of cells from clinically normal individual cattle to produce and respond to IL-2 was investigated as a measure of specific cell-mediated immune response. Cells from the majority of animals (6/7 in a representative experiment) could produce IL-2 in response to mitogen or a specific antigen, Bovine Herpesvirus 1 (BHV-1). Proliferation of lymphocytes from the majority of low responding animals (2/3 and 4/4 in separate experiments) could be restored to a level similar to high responders by the addition of exogenous IL-2 after endogenous IL-2 depletion. IL-2 receptor expression was indirectly assessed by the ability of activated cells to absorb IL-2. One individual's cells were incapable of absorbing exogenous IL-2 and failed to proliferate indicating a lack of activation and expression of receptors. In addition, exogenous IL-2 was able to enhance proliferation of both high and low responders in the presence of endogenous IL-2. These results suggest that proliferation of bovine peripheral blood mononuclear cells is dependent on the presence of IL-2. In addition, IL-2 production can be used to measure specific cell-mediated immune responses.
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PMID:Detection of impaired T cell-mediated immune responses to herpesvirus (BHV-1) in cattle. 302 Jul 71

Interleukin 2 (IL-2) receptors are expressed on activated T cells and in select T-cell leukemias. Recently, it has been demonstrated that at least two classes of receptor for IL-2 exist with markedly different affinities for ligand. All known biological actions of IL-2 have been correlated with occupancy of high-affinity sites; the function of the low-affinity sites remains unknown. Receptor-mediated endocytosis is the primary means of internalization of cell-surface receptors and their ligands. The internalization of IL-2 bound to high- and low-affinity receptor sites was studied in a human T-cell lymphotrophic virus type 1 (HTLV-1)-infected human T-cell leukemia cell line and in a cloned murine cytotoxic T-cell line (CTLL). Internalization of IL-2 occurred only when bound to high-affinity sites. In addition, an anti-receptor antibody (anti-Tac), which binds equally well to high- and low-affinity sites, demonstrated no detectable internalization. The implications of these findings as they relate to IL-2 receptor structure and function are discussed.
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PMID:Only high-affinity receptors for interleukin 2 mediate internalization of ligand. 308 98

Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T-cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined.
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PMID:Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity. 309 9

Interleukin 2(IL-2), a lymphokine that is produced by helper T cells, plays a key role in the proliferation of T lymphocytes by interacting with a specific cell surface receptor. Recent studies demonstrated that the IL-2 receptor exists in two forms having different affinities to the ligand and the growth signal seems to be delivered by IL-2 bound to the high affinity, but not the low affinity, receptor. In man, both forms of the IL-2 receptor can be recognized by a monoclonal antibody, anti-Tac. Using this antibody, a cDNA that encodes Tac antigen has been cloned from ATL-derived T cell line. Transfection of the cloned cDNA into mammalian non-T cells, however, resulted in the expression of only a non-functional, low affinity IL-2 receptor. This observation raised a question whether or not the cloned cDNA for Tac antigen actually encodes the functional, high affinity IL-2 receptor. In order to clarify this problem, Tac antigen cDNA was obtained from human PBL cDNA library. This cDNA was connected to RSV-LTR and was transfected into mouse thymoma derived T-cell line EL4, and L929 fibroblast. Then transformants that constitutively express Tac antigen were established. IL-2 binding assay demonstrated that EL4 transformants expressed high affinity as well as low affinity human IL-2 receptor. In contrast, L929 transformants expressed only a low affinity receptor. The growth of the EL4 transformants harboring the high affinity human IL-2 receptor was inhibited by virtue of the specific interaction of the receptor with human, but not mouse, recombinant IL-2. These results demonstrate: the cloned cDNA dose encode a functional IL-2 receptor, the affinity of the IL-2 receptor is variably modified by post-translational events and 3. IL-2/receptor interaction leads to the reversal of the cell growth in EL4 cells. The reconstitution system described here will be of great use in elucidating the mechanism of T cell growth.
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PMID:[Expression of functional human interleukin 2 receptor in mouse cells by using gene transfection]. 309 55

These studies described were designed to determine whether interleukin 2 (IL-2) inhibits lymphocyte migration. The human lymphoblastoid cell line QIMR-WIL was used as an indicator of lymphocyte migration inhibition. Interleukin 2 inhibited QIMR-WIL migration in a dose-dependent manner, high doses of IL-2 (100 units) being strongly inhibitory, and low doses (12.5 units) less inhibitory. Purified natural IL-2 and recombinant IL-2 both inhibited QIMR-WIL migration. The effect of IL-2 on lymphocyte migration was specific. When the IL-2 receptors were blocked with anti-Tac (anti-IL-2 receptor) antibodies, the inhibitory effect of IL-2 was significantly reduced. Similarly antibody to IL-2 blocked the inhibitory effect of IL-2. Lymph node lymphocytes were also used as indicator cells in migration studies and IL-2 inhibited their motility. These data suggest a role for IL-2 in inhibiting lymphocyte migration similar to that of lymphocyte migration inhibition factor produced by antigen- or mitogen-stimulated T lymphocytes. While it is widely recognized that lymphocyte motility can be reduced by lymphocyte migration inhibition factor, these data indicate that IL-2 can also reduce lymphocyte motility.
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PMID:Inhibition of lymphocyte motility by interleukin 2. 310 35

Phorbol ester phorbol myristate acetate (PMA) induces proliferation in nonmalignant human B cells and B cells from a patient with B prolymphocytic leukemia (B-PLL). Mitogen-free T cell-derived conditioned medium acts synergistically with PMA in inducing proliferation of B-PLL cells but does not enhance the PMA-stimulated outgrowth of nonmalignant B cells. Interleukin 2 (IL-2) has no effect on the outgrowth of B-PLL cells, and monoclonal antibodies against the IL-2 receptor do not influence the response to PMA and conditioned medium. Recombinant interferon-gamma (IFN-gamma), in contrast, is a potent enhancer of PMA-induced proliferation of B-PLL cells. With gel filtration techniques and with the use of anti-IFN-gamma antibodies, it is shown that IFN-gamma in the conditioned medium is responsible for the observed increase in B-PLL cell proliferation. Preincubation of B-PLL cells with IFN-gamma induces responsiveness to PMA, whereas IFN-gamma alone had no effect on these cells when pretreated with PMA. The combined data show that, in the presence of PMA, native and recombinant IFN-gamma are growth factors for B cells from a B-PLL patient and that IL-2 is not involved in this process.
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PMID:Induction of proliferation of B prolymphocytic leukemia cells by phorbol ester and native or recombinant interferon-gamma. 311 13

Interleukin 2 (IL-2) binds to its receptors with three distinct affinities, with Kd values of 10(-11) M (high), 10(-9) M (intermediate) and 10(-8) M (low). IL-2 responding cells express two proteins that bind IL-2, i.e. a 55 x 10(3) Mr protein (p55 or L chain), which has classically been known as the IL-2 receptor and a second 75 x 10(3) Mr chain (p75 or H chain) with intermediate affinity. Experiments were performed to clarify the mechanism of the high-affinity site formation. Crosslinking of human IL-2 with the high-affinity sites of human T lymphocytes yielded a 150 x 10(3) Mr ternary complex consisting of IL-2, L and H chains. The ternary complex with human IL-2 was formed on EL/Tac 3 cells expressing human L and murine H chains, although human IL-2 was unable to bind to the parental EL-4 cell, which does not express human L chain. The high-affinity ternary complex was stable during solubilization and fractionated by gel-filtration chromatography, and the numbers of these complexes were quantified by this method. The number of high-affinity sites on the CT/hR-1 cells, which express the human L, murine L and murine H chains, was almost constant even when either the human or murine L chain was blocked by specific antibodies in agreement with a previous observation. These results indicate that the L and H chains do not form a stable binary complex by themselves and that IL-2 binding induces the formation of the stable high-affinity ternary complex.
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PMID:Molecular mechanism for the formation of the high-affinity complex of interleukin 2 and its receptor. 313 61

The present study was undertaken to assess the efficacy of recombinant Interleukin 2 (rIL-2: S-6820) in treatment of superficial bladder tumors. Three intratumor injections at a dose of 5 x 10(5) units/day via urethra, were performed every other day under endoscopic control in 12 patients with superficial bladder cancer. On the 15th day after completion of the series of injections, the tumor had disappeared in one patient and 50% regression over was observed in two other patients. Therefore, the response rate to the rIL-2 treatment in our study was 25.0%. Each tumor which responded to the therapy, was single, small and low grade. In the peripheral blood of the 12 patients, an increase in IL-2 receptor-positive lymphocytes and augmentation of natural killer activity were detected after the rIL-2 intratumor injection. There were no serious side effects except for moderate fever in our study.
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PMID:[The efficacy of recombinant interleukin 2 in local treatment of superficial bladder tumors]. 326 44

In order to study the possible role of the T-lymphocyte growth factor, Interleukin 2 (IL-2), and/or of the IL-2 receptor in the autonomous growth of leukaemic cells, 15 mouse leukaemic cell lines of various aetiology were analyzed for (i) IL-2 receptor expression and (ii) for the capacity to secrete IL-2. Several but not all of the cell lines tested were IL-2 receptor positive. The cells constitutively expressing IL-2 receptors at their surface could not be stimulated to secrete IL-2. Cell producing and secreting IL-2 did not express detectable amounts of IL-2 receptors at their surface. It has been demonstrated that proliferation of the leukaemic cells was independent of exogenous IL-2. The monoclonal anti-IL-2 receptor antibody AMT-13 inhibited IL-2 dependent proliferation of activated normal T-lymphocytes but failed to inhibit the growth of IL-2 receptor expressing leukaemic cells. The results argue against the autocrine stimulation hypothesis but do not exclude the possibility of involvement of functionally altered IL-2 receptors on autonomous cell growth.
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PMID:Studies on interleukin 2 receptor expression and IL-2 production by murine T cell lymphomas. 391 77


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