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

Human B cells appropriately activated by a B cell mitogen are rendered susceptible to human Interleukin 2 (IL-2) as demonstrated with recombinant human IL-2 (rec. h IL-2). They show increased proliferation and drastically enhanced immunoglobulin secretion. Susceptibility to IL-2 is accompanied with the expression of the IL-2 receptor (Tac antigen) on B cells. The data suggest that IL-2 is one of the lymphokines directly involved in the activation of B lymphocytes.
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PMID:Recombinant human interleukin 2 acts as a B cell growth and differentiation promoting factor. 392 56

Patients with active Hodgkin's disease (HD) often demonstrate an impaired T-cell proliferative response to phytohemagglutinin (PHA). The present study examined if interleukin regulation of the PHA response was defective in HD. The Hodgkin's PHA response was impaired at all concentrations of PHA utilized. Indomethacin increased the proliferative response but did not bring it to control levels. Stimulation of the cells with both PHA and irradiated Ia+ B cells normalized proliferation despite identical PGE2 concentrations as in the PHA alone cultures. Hodgkin's monocytes produced normal amounts of interleukin 1 (IL-1). Interleukin 2 (IL-2) production by Hodgkin's T cells was decreased in the PHA stimulated cultures, but was normal in the PHA and Ia+ cell stimulated cultures. In response to PHA stimulation alone, Hodgkin's T cells expressed less IL-2 receptor than control cells. The data suggest the diminished PHA response in HD is due to impaired IL-2 production resulting in diminished IL-2 receptor expression. However, when an Ia+ cell source is added to PHA as an additional stimulator, both TCGF production and proliferation are normalized. Monocytes serve to modulate the magnitude of the PHA response through production of both interleukin 1 and PGE2. However, in the presence of sufficient IL-2 production the influence of monocytes is minimized.
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PMID:Impaired interleukin regulation of the phytohemagglutinin response in Hodgkin's disease. 392 53

Interleukin 2 provides a signal for the proliferation and differentiation of several classes of immune cells, including activated T cells, natural killer cells and certain activated B cells. The responses to this lymphokine result from its interaction with a high-affinity cell surface receptor. Several structural features of the IL-2 molecule are essential for its functional integrity. For example, an intramolecular disulfide bridge connecting cysteine residues in positions 58 and 105 maintains an active conformation of the molecule. In addition, antibodies directed against epitopes defined by amino acids 8-27 and 33-54 are capable of directly blocking the physiological response. Amino acids in or near these regions may form part of the receptor binding site of IL-2. The receptor for IL-2 exists in both high and low-affinity states. Physiological responses correlate with binding to the high-affinity form of the receptor as determined by anti-IL-2 antibody competition curves. Expression of the cDNA corresponding to the receptor protein in mouse L cells, however, indicates that this protein alone is incapable of high-affinity interaction with IL-2. Thus, the high-affinity conformation of the receptor may entail the interaction of the ligand-binding component with an additional receptor subunit(s). The availability of pure ligand and receptor as well as antibody reagents to both these components make the IL-2 receptor system an ideal model for dissecting an immune response at the molecular level.
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PMID:Interleukin 2 and its cell-surface receptor. 393 74

We describe the production and some of the properties of a monoclonal antibody which inhibits binding of Interleukin 2 (IL-2) to rat T lymphoblasts as well as the capacity of these lymphoblasts to proliferate in response to IL-2 of rat or murine origin. According to these criteria, the antibody seems to be directed against an antigenic determinant on the IL-2 receptor. The antibody, obtained from hybridomas derived from mice immunized with phorbol-myristate-acetate-pulsed rat T lymphoblasts, exhibited species specificity, indicating that IL-2 receptors of various species are not necessarily identical, even if they can respond to IL-2 from different species.
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PMID:Studies on T lymphocyte activation. II. Monoclonal antibody inhibiting the capacity of rat T lymphoblasts to absorb and to respond to IL-2: an anti-IL-2 receptor antibody? 660 Jul 7

Purified Interleukin 2 (IL-2), free of interferon (IFN), significantly enhanced NK activity of normal human peripheral blood mononuclear cells (PBMC). This enhancing activity was absorbed by IL-2 receptor-bearing cells but was not blocked by antibody to alpha-IFN. IFN in the culture supernatants was greatly increased after stimulation with poly(I:C) plus IL-2. There was less IFN produced by either modulator acting alone. Stimulation of PBMC with IL-2 and/or poly(I:C) increased the proportion of OKM1+ cells and anti-Leu-7+ cells. When cells expressing either surface antigen were specifically lysed to deplete NK, cytotoxic activity could be restored by overnight incubation in IL-2. This result suggests that IL-2 stimulates the development of NK cells from precursors that lack cell surface OKM1 or Leu-7. IL-2 acted directly on large granular lymphocytes and did not require the presence of adherent cells. These results suggest that IL-2 may act synergistically with other IFN inducers and may play an important role in the regulation of NK cells.
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PMID:Interleukin 2 enhances natural killing of normal lymphocytes. 660 76

Interleukin 2 (IL-2) immunotherapy has met with limited success in the treatment of renal cell carcinoma (RCC) and malignant melanoma (MM). However, non-responders still account for up to 80% of those patients receiving IL-2. A high concentration of soluble IL-2 receptor (sIL-2R) is commonly found in the blood of such patients. We investigated the possibility that high sIL-2R concentration pretreatment may interfere with the bioavailability of IL-2. The mean concentration of sIL-2R in plasma from patients with MM, RCC and head and neck cancer was 3378 U ml-1, 8778 U ml-1 and 764 U ml-1 respectively, compared with 1315 U ml-1 in plasma from healthy volunteers. Inclusion of plasma from patients with RCC and MM patient plasma in cytotoxic T-lymphocyte leukaemic (CTLL) cell/IL-2 assays inhibited the ability of CTLL cells to respond to IL-2, and an inverse correlation was found between the concentration of sIL-2R and the growth response of CTLL cell to IL-2 (r = -0.86, P = 0.003). Plasma with soluble IL-2R concentrations greater than 3000 U ml-1 produced a reduction in cell growth of more than 50% when included in CTLL IL-2 assays. The addition of increasing concentrations of IL-2 to cultures containing suppressive plasma failed to restore CTLL cell growth response to normal. Failure to saturate sIL-2R by exogenous IL-2 addition therefore suggests that another factor, initially present at a concentration similar to the sIL-2R concentration, is responsible for the observed effect. Determination of the suppressive effect of patient plasma as presented here may allow more effective IL-2 dosing schedules.
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PMID:Increased soluble interleukin-2 receptor concentration in plasma predicts a decreased cellular response to IL-2. 764 Feb 31

Interleukin 2 (IL-2) activates natural killer cells and generates lymphokine-activated killer (LAK) cell-mediated cytotoxicity. In "adoptive immunotherapy," a combination of LAK administration and IL-2 infusion was found to be effective therapy for some tumors and ineffective for others. Here we report a novel function for IL-2, its ability to protect tumor cells (cell lines obtained from hairy cell leukemia patients) against LAK activity. The protective effect induced by IL-2 is similar to that induced by interferon (IFN). Protection by both cytokines requires new mRNA/protein synthesis; both IL-2 and IFN reduce the ability of tumor target cells to trigger LAK effector cells following binding between these two types of cells. However, endogenous IFN is not the mediator of the IL-2 protective effect against LAK activity since monoclonal antibodies against IFN-alpha and IFN-gamma did not abolish the protective effect of IL-2. In addition, IL-2 does not induce the expression of class I major histocompatibility complex antigens on the target cell surface, believed to be the signal for the IFN-induced protection against natural killer and LAK activities. Finally, leukemic cells resistant to IFN-alpha did respond to IL-2 treatment and became less sensitive to LAK cytotoxicity. Thus the ability of IL-2 to protect tumor cells from LAK activity may explain the lack of response to adoptive immunotherapy in tumors that express the IL-2 receptor.
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PMID:Interleukin 2 protects hairy leukemic cells from lymphokine-activated killer cell-mediated cytotoxicity. 768 24

Interleukin 2 (IL-2) is one of the major cytokines produced by T lymphocytes in response to antigen. It is a potent growth and differentiation factor for several cell-types and is structurally related to the four-helix bundle family of cytokines. Mutation of residue Phe42 to Ala abolishes binding to the alpha chain of the tri-partite IL-2 receptor. The three-dimensional structure of the F42A mutant IL-2 has been calculated by two dimensional NMR methods and compared to a structure of wild-type IL-2 determined by X-ray crystallography. The overall topology of the two structures is the same. The main differences between the structures are within the ill-defined loops connecting the helices and the region of the protein that is believed to interact with the alpha-chain of the receptor. Thus, the mutation of Phe42 to Ala does not perturb the overall three-dimensional structure of IL-2, and does not appear to change the putative binding sites for the beta and gamma chains of the receptor. The structural differences observed in this mutant suggest that the replacement of Phe42 with Ala causes the re-orientation of neighbouring side-chains that are also involved in binding the alpha-chain of the receptor.
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PMID:The solution structure of the F42A mutant of human interleukin 2. 772 44

In hypothyroid patients serum soluble IL-2 receptor levels showed scattered and conflicting results. In our report we studied circulating soluble interleukin 2 receptors in 22 patients with hypothyroid autoimmune thyroiditis before L-thyroxine treatment and when the patients became euthyroid. The mean of soluble Interleukin 2 receptor levels in the hypothyroid state was 48.6 pmol/l (95% confidence interval, 45.6-51.5) statistically lower than in the controls (95% confidence interval, 86.4 pmol/l, 83.3-89.4) (p < 0.0001). When the patients became euthyroid during L-thyroxine treatment, soluble Interleukin 2 receptor levels increased, showing mean values comparable to the controls. A positive high correlation (p < 0.001) was observed between soluble Interleukin 2 receptor levels and thyroxine free levels in the hypothyroid as well as in the euthyroid state and between soluble Interleukin 2 receptors and the mean weekly L-thyroxine dose. Our study confirmed that in the hypothyroid state, the behaviour of soluble Interleukin 2 receptors is anomalous as compared to other autoimmune diseases. In fact a strict relationship exists between the levels of thyroid hormones and soluble Interleukin 2 receptors but not between the latter and antithyroid antibodies. These results agree with those supporting a role for thyroid hormones in the regulation of the immune system. They also suggest that the measurement of soluble Interleukin 2 receptors could be used as a marker of the peripheral action of thyroid hormones.
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PMID:Circulating soluble IL-2 receptor levels are low in patients with hypothyroid autoimmune thyroiditis. 787 52

Interleukin 2 (IL-2) stimulated activation of the 42-kD extracellular signal-regulated kinase 2 (Erk2) in murine IL-3-dependent cells, expressing either high or intermediate affinity IL-2 receptors. Activation was both rapid, occurring within 5 min of IL-2 addition, and prolonged, remaining elevated for 30 min. Activation of Erk2 appeared to be necessary for IL-2 stimulation of proliferation, as deletion of a region of the cytoplasmic domain of the IL-2 receptor beta chain, essential for IL-2 stimulation of proliferation, abolished Erk2 activation by IL-2. Furthermore, cells that had been deprived of cytokine for 24 h were then refractory to IL-2 stimulation of both Erk2 activity and proliferation. However, elevation of Erk2 activity was not sufficient to stimulate proliferation, as protein kinase C activation stimulated Erk2 activity but not DNA synthesis. Also, cells exposed to IL-2 in the presence of rapamycin showed full Erk2 activation but not DNA synthesis. These data suggest that IL-2 must stimulate both Erk2 activity and a further pathway(s) to trigger cell proliferation.
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PMID:Interleukin 2 activates extracellular signal-regulated protein kinase 2. 837 45


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