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

Peripheral blood mononuclear cells cultured in vitro with interleukin 2 (IL-2) become cytolytic towards both autologous and allogeneic tumor cells. We report here that IL-1 synergizes with IL-2 in serum-free conditions to produce increased (1.3-286-fold) lymphokine-activated killer (LAK) activity. The most dramatic synergy is seen with low IL-2 concentrations (10 U/ml, 222 pM) and 50-250 U/ml IL-1 alpha or beta. Kinetics of addition experiments demonstrate a specific requirement for IL-1 at or before addition of IL-2 to the culture. We postulate that one of the mechanisms whereby IL-1 augments LAK activity is by rendering LAK-precursors more responsive to IL-2. Up-regulation of the IL-2 receptor beta chain (Tac) and increased [3H]thymidine incorporation in cultures containing IL-1 and IL-2 support this view. In some instances, IL-1 alone is capable of maintaining/generating a small degree of cytolytic activity. Collectively, our data demonstrate that IL-1 is capable of interacting with low dose IL-2 to significantly augment LAK activity, potentially playing an important role in the early stages of LAK activation and differentiation. Because synergy is observed with dramatically reduced IL-2 concentrations, this system may offer an alternative approach to high dose IL-2 therapy for the treatment of neoplastic disease.
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PMID:Synergy of human recombinant interleukin 1 with interleukin 2 in the generation of lymphokine-activated killer cells. 278 41

Uncertainty has existed as to whether a T-cell deficiency exists in human immunodeficiency virus (HIV) infection different from that inherent in the reduced T-cell numbers characteristic of the disease. Heretofore, methods for measuring T-cell responses in patients have been carried out with systems requiring monocytes as accessory cells. In the presence of high concentrations of interleukin-2, however, highly purified T cells respond in a monocyte-independent fashion to antibody reactive with the CD3 component of the antigen receptor complex Ti/CD3. Highly purified T cells of HIV-infected patients responded subnormally in this anti-CD3/IL-2 system, even in the case of patients who were asymptomatic or had only lymphadenopathy. The defective T-cell responses occurred over a wide range of concentrations of the anti-CD3. Neither poor IL-2 receptor function as reflected by responses to limiting dilutions of IL-2 nor IL-1 receptor function as defined by incremental proliferation when IL-1 is added accounted for this defect, which also correlated poorly with T4 and T8 numbers. These results suggested that the T-cell abnormality was closely related to Ti/CD3 function, was not specifically or restrictively associated with T4 cells, and was not due to defective IL-2- or IL-1-receptor functions. The amount of HIV RNA in 10(5) T lymphocytes from the patients amounted to less than that found in one cell of a standard HIV infected laboratory cell line (CEM), using slot-blot hybridization. Thus the T-cell deficiency we have observed was not likely to be due directly to cell killing by HIV resident in the T4 cells. Other factors may be important in inducing the immunodeficiency, some of which are discussed.
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PMID:Impairment in T-lymphocyte responses during early infection with the human immunodeficiency virus. 278 31

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.
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PMID:Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera. 278 62

An inhibitor of the murine interleukin 2 (IL-2) dependent cell line (CTLL-2) has been demonstrated in sera from healthy subjects as well as in sera and synovial fluid from patients with inflammatory arthritides. This inhibitor inhibits the mitogenic response of normal peripheral blood mononuclear cells and seems to be primarily due to impaired IL-2 production. The inhibitor does not appear to bind to IL-2 or the IL-2 receptor. This inhibition can be reversed with IL-2 but not interleukin 1. These observations may apply to the defects in IL-2 production and response demonstrable in rheumatoid arthritis and other autoimmune disorders.
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PMID:Interleukin 2 and interleukin 2 inhibitors in human serum and synovial fluid. I. Characterization of the inhibitor and its mechanism of action. 278 2

In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.
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PMID:Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells. 217 41

The cytokine interleukin-1 plays an important role in the induction of IL-2 secretion and IL-2 receptor expression. The events that follow binding of IL-1 to its receptor are not known. We found that in a purified T cell population (comprising the Lyt2- and L3T4- T cells) IL-1 in the absence of antigen or mitogen induced strong proliferation and de novo expression of IL-2R light chain mRNA. This was accompanied by high affinity IL-2 binding. Production of IL-2 or IL-2 mRNA was not detected under these conditions. As a model system for IL-1 action two EL4 subclones were isolated. EL4 5D3 responded to IL-1 by augmentation of PMA induced IL-2 secretion and IL-2R expression. EL4D6/76 bound IL-1 with the same affinity but did not respond. We found that this line was unable to internalize surface bound IL-1. The finding suggests that in T cells internalization of IL-1 is required for its activity.
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PMID:Activation of T cells by interleukin 1 involves internalization of interleukin 1. 278 20

Specific immunoassays were used to measure IL-1 peptides in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and in the serum of age-matched healthy controls. Patients with RA had raised levels of both IL-1 beta and IL-1 alpha in their sera compared to controls. Synovial fluid levels of IL-1 beta significantly correlated with immunoreactive IL-2 and soluble IL-2 receptor (sIL-2R). In addition, incubation of synovial fluid MNC with human recombinant (hr) IL-1 caused a dose-dependent increase in the level of sIL-2R in the cell supernatant. Finally, production of IL-1 beta and IL-6 from RA peripheral blood (PB) and synovial fluid (SF) MNC was examined. PBMNC spontaneously produced low levels of IL-1 beta and IL-6 that were augmented by the addition of hr IL-1 alpha. In contrast, SFMNC spontaneously produced high levels of IL-1 beta but only low levels of IL-6, again this production was augmented by the addition of hr IL-1 alpha. Taken together, the data suggests that IL-1 potentiates immune responses within the joint.
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PMID:Interleukin 1 in rheumatoid arthritis: potentiation of immune responses within the joint. 278 25

We studied interleukin 1 (IL-1) and interleukin 2 (IL-2) production in unstimulated and stimulated cultures from 27 young diabetic patients and 21 age-matched healthy subjects. In unstimulated cultures monocytes from newly diagnosed patients produced significantly higher levels of IL-1 than controls. In lipopolysaccharide (LPS)-stimulated cultures, IL-1 production in patients with fresh and long-standing diabetes was no different from that of controls. IL-2 production was low or absent in unstimulated cultures from insulin-dependent diabetes mellitus (IDDM) patients and controls. In phytohaemagglutinin (PHA)-stimulated cultures both patient groups produced significantly less IL-2 than controls. No correlation was observed between IL-1, IL-2 production and HbA1 levels or the presence of HLA-DR3 or DR4. Our data on "spontaneous" IL-1 production support the hypothesis that monocytes from some newly diagnosed IDDM patients may circulate in a "preactivated" state. The low levels of IL-2 might be explained by an abnormal consumption or by the presence of increased soluble IL-2 receptor levels or by a serum factor which interferes with IL-2 production. Alternatively, it may be a genetically determined trait.
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PMID:Alterations of in vitro interleukin 1 and 2 in diabetic children. 279 22

Chemiluminescence and flow cytometry, employing a number of monoclonal antibodies, was used to investigate activation of immunocompetent cells in the blood and peritoneum of patients treated with CAPD. Increased expression of HLA-DR and RFD7, both markers of macrophage maturation, was observed on peritoneal macrophages, 78% and 33.5% cells positive, when compared to blood monocytes, which were 46% and 5.3%, respectively (P less than 0.001). Macrophage chemiluminescent response to opsonized zymosan was greater than that of circulating blood monocytes in CAPD patients, whereas the inverse was true for normal controls. Enhanced expression of IL-2 receptor and surface IgG by peritoneal macrophages were 24.9% and 65.3% cells positive compared with monocytes, 5.7% and 12.3% (P less than 0.01), and also suggests their activation. There was a marked increase in the HLA-DR expression by peritoneal lymphocytes from CAPD patients (32% cells positive) compared with those from CAPD blood (13.8%), normal blood (11.3%) and normal peritoneal fluid (14.5%), P less than 0.001. This was partially accounted for by increased numbers of B cells (18%) and activated T cells bearing HLA-DR. TFR and IL-2 receptor expression by CAPD peritoneal lymphocytes was similar to that of blood lymphocytes, implying the lack of an organized immune response within the peritoneum. Taken together, these results suggest that peritoneal macrophages from CAPD treated patients have features of maturation and activation, while changes in the lymphocyte populations are compatable with the actions of IL-1, indicating activity of the cellular immune system within the peritoneum.
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PMID:Activation of immunocompetent cells in the peritoneum of patients treated with CAPD. 281 Oct 64

Many cytokines have been documented to have a multiplicity of biological effects by acting on a variety of cells. In order to determine whether human BCGF-II acts on any cells in addition to normal B cells, the effect of human BCGF-II on murine thymocytes, human peripheral blood T cells, a human natural killer-like cell line, YT, and Epstein-Barr virus (EBV)-transformed B-cell lines was further examined. BCGF-II augmented incorporation of [3H]thymidine by murine thymocytes in combination with suboptimal doses (0.5 microgram/ml) of concanavalin A (Con A) but not at lower doses (0.1 microgram/ml) of Con A, a concentration usually used for interleukin 1 (IL-1) assays. BCGF-II could not induce proliferation or Tac antigen (Ag) expression on normal peripheral blood T cells stimulated with OKT3 antibody. Both proliferation and Tac Ag expression on YT cells were also augmented by BCGF-II. BCGF-II induced both high- and low-affinity IL-2 receptor (IL-2R) on YT cells as determined by 125I-IL-2-binding assay. Two of seven EBV-transformed B-cell lines tested (ORSON and AUM cells) in response to BCGF-II exhibited augmentation of proliferation and cell surface Tac Ag expression. BCGF-II in the presence of low doses (0.1 microgram/ml) of phorbol myristate acetate (PMA) also induced Tac Ag mRNA (3.5 and 1.5 kb) in these B-cell lines. The IL-2R induced on these B-cell lines, however, consisted mostly of low-affinity receptors. Both Tac Ag and its mRNA in these B-cell lines were not induced by Forskolin but by PMA, suggesting that this induction may involve protein kinase C. The present study shows that human BCGF-II can stimulate YT cells, murine thymocytes, and some EBV-transformed B-cell lines but not peripheral blood T cells. Consequently, BCGF-II can induce the growth and differentiation of a number of cell types in addition to normal B cells.
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PMID:A major 50-kDa human B-cell growth factor-II induces both Tac antigen expression and proliferation by several types of lymphocytes. 282 95


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