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

A factor enhancing proliferation of human peripheral blood lymphocytes (PBL) was identified in the culture supernatant of a human myeloid cell line HL-60 after ion exchange separation. Partially purified lymphocyte growth enhancing factor (LGEF) was found to enhance mitogen-stimulated PBL or purified T cell proliferation in a dose dependent fashion. LGEF alone did not stimulate PBL or T cell proliferation and its activity was dependent on the presence of mitogen. LGEF mediated T cell proliferation was neither accompanied by an increase in the level of IL-2 receptor expression, nor was dependent on the presence of monocytes. In ELISA assay antibodies against IL-1, IL-2, IL-3 and IL-6 did not recognize the LGEF preparation. The comparison of LGEF with other lymphokines is discussed.
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PMID:Identification of a co-stimulatory factor for human T cell proliferation. 200 56

We investigated the induction of tissue factor by lymphokines in human monoblastic leukemia cell lines (U937) and leukemic cells from AML (acute myelogenous leukemia) patients. After incubation for 24 h, IL-2 enhanced the intracellular tissue factor 15-fold with U937 cells, and GM-CSF enhanced it 6-fold. In contrast, other lymphokines, such as IL-1-alpha, IL-1-beta, IL-3, IL-4 and G-CSF, did not affect the activity of tissue factor. The leukemic blasts, depleted of T-lymphocytes, taken from five out of 16 AML patients showed a 2.5-14-fold increase in the activity of tissue factor per cell following incubation with 200 u/ml of IL-2 for 72 h. The IL-2 induced tissue factor activity more markedly than GM-CSF. Tissue factor stimulation by IL-2 did not correlate with the expression of the IL-2 receptor, Tac, but correlated well with FAB classification of AML cells. IL-2 responders were found in M4 and M5 subtypes only, but not all M4/M5 leukemias responded to IL-2. These findings indicate that IL-2 can mediate the tissue factor induction in the monocytic type of AML and the effect is not mediated by Tac receptors. This may shed a new light on our understanding of hypercoagulability in acute monoblastic leukemia.
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PMID:Induction of tissue factor by interleukin-2 in acute myelogenous leukemia (AML) cells. 208 39

Full length cDNAs encoding the human and murine p70 genes were isolated using polymerase chain reaction (PCR) and conventional cDNA library screening techniques, respectively. To validate their functional potential, expression vectors containing human, murine and chimeric human/murine p70 cDNAs were transfected into the murine IL-3-dependent cell line FDC-P1. Transfected cells expressed a combination of high and low-affinity IL-2 binding sites while parental cells displayed only the low-affinity sites associated with expression of endogenous p55 IL-2 receptor chains. The role of the transfected p70 chains in formation of the high-affinity receptor sites was confirmed by the finding that the species-specific inhibitory antibody TU27 blocked high-affinity binding to human p70 and chimeric human/murine p70-expressing cells while having no effect on cells transfected with the murine p70 cDNA construct. As consequences of the expression of the transfected p70 chains, the cells responded to IL-2 with increased levels of endogenous p55 receptor subunit and both short and long-term proliferation. These studies substantiate the role of the p70 receptor chain in functional responses to IL-2 and provide a model system for future dissection of the structure/function relationships of the IL-2 receptor.
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PMID:Functional expression of native and chimeric human and murine IL-2 receptor p70 chains in an IL-3-dependent murine cell line. 209 Aug 77

The regulation of rat lymphokine-activated killer (LAK) cell generation from their purified precursors using various cytokines was studied. Several important findings emerged from this study. These include: (i) interleukin-2 (IL-2), but not any other cytokine tested, is pivotal for the development of LAK cells; (ii) transforming growth factor beta 1 (TGF-beta) inhibits IL-2-induced LAK cell differentiation, but not proliferation, regardless of the dose of IL-2 used; (iii) interferon-gamma (IFN-alpha) is inhibitory for LAK cell proliferation, but not differentiation; (iv) tumour necrosis factor-alpha (TNF-alpha) or IFN-gamma synergize with a low but not a high concentration of IL-2; (v) TNF-alpha reverses the anti-differentiative activity of TGF-beta 1 in the presence of a high, but not a low, concentration of IL-2; (vi) anti-p55 IL-2 receptor (R) is not inhibitory for LAK cell development but, on the contrary, a low concentration of this antibody synergizes with IL-2; (vii) IL-1 alpha, IL-1 beta, IL-3, IL-4, IL-6, IFN-alpha. TNF-alpha, or TGF-beta 1 do not affect LAK cell function; and (viii) IL-2 may provide two separate signals for LAK precursors: one is proliferative and the other is differentiative.
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PMID:Differential effects of various cytokines on the generation of rat LAK cells from their purified precursors. 211 78

Lymphokine-dependent T cell proliferation is regulated in part by the cell surface expression of high affinity interleukin-2 receptors (IL-2R). The functional, high affinity form of the IL-2 receptor is comprised of two ligand binding components, IL-2R alpha (Tac, p55) and IL-2R beta (p70/75). In the absence of the other subunit, IL-2R alpha and IL-2R beta bind ligand with only low or intermediate affinity, respectively. The inducible and transient expression of IL-2R alpha regulates the display of high affinity receptors, while IL-2R beta appears to contribute importantly to growth signal transduction. Although the primary structure of both receptor chains has now been elucidated, the mechanism of growth signal transduction through the high affinity IL-2R remains undefined. Of note, IL-2R beta belongs to a novel family of cytokine receptors including the binding proteins for IL-3, IL-4, IL-6, erythropoietin, and granulocyte-macrophage colony-stimulating factor. These various receptors may well utilize a common intracellular signalling pathway.
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PMID:The human interleukin-2 receptor: insights into subunit structure and growth signal transduction. 212 4

We have isolated and studied two alloreactive, T4+, human lymphocyte clones that release interleukin 2 (IL-2) and interleukin 3 (IL-3) bioactivities upon stimulation with IL-2, alloantigen, or Sepharose-conjugated antibodies directed against the T3 protein. Anti-IL-2 receptor monoclonal antibodies block IL-2-, alloantigen-, or anti-T3-stimulated IL-3 release. Hence, release of IL-3 activity in each circumstance is rigorously dependent upon activation of the IL-2 receptor. Even low, nonmitogenic concentrations of recombinant IL-2 stimulated IL-3 release.
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PMID:Interleukin 2-dependent release of interleukin 3 activity by T4+ human T-cell clones. 241 52

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.
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PMID:FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. 244 22

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.
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PMID:Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients. 250 74

Addition of recombinant interleukin-2 (rIL-2) to normal adult murine thymocytes in vitro as the only exogenous stimulus leads to a dose-dependent mitogenic response characterized by two distinct dosage kinetic components. The high-affinity IL-2 thymocyte response is mounted by in vivo-activated (IL-2 receptor light chain positive) thymocytes, while the low-affinity IL-2 response, of larger amplitude, is carried out by resting thymocytes. Addition of IL-2 to thymocytes also triggers intense IL-3 secretory responses with both high and low IL-2 affinity components. Addition of high IL-2 dosages to thymocyte bulk cultures results in a dramatic increase in IL-2 responsiveness for both proliferation and IL-3 secretion on a per viable cell basis and with tightly coupled temporal kinetics. The low-affinity component of IL-2-proliferative and IL-3-secreting responses is carried out by resting mature CD4+ thymocytes, as assessed by negative selection with monoclonal antibodies (mAb) plus complement. The mechanism of resting thymocyte activation by high doses of IL-2 is partially characterized. Depletion of endogenous thymus-adherent cells abolished both proliferation and IL-3 secretion, and addition of splenic accessory cells or peritoneal macrophages to depleted thymocytes restored IL-2 responsiveness. Mature CD4+ thymocytes spontaneously form rosettes with adherent accessory cells, while CD8+ thymocytes do so with much less efficiency. Rosette formation of CD4+, but not of CD8+ thymocytes, can be blocked by anti-CD4 mAb GK1.5. At the same dosage as it prevents rosette formation, mAb GK1.5 also blocks the low-affinity thymocyte response to IL-2. The high-affinity IL-2 response is completely resistant to the action of cyclosporin A (CsA), but the low-affinity IL-2 response, although of much larger amplitude, can be almost completely suppressed by CsA. Together, these results demonstrate that resting CD4+ thymocytes can be induced to proliferation and lymphokine secretion by IL-2 alone in a process that is dependent on interaction with accessory cells, involves CD4 adhesion molecules and triggers activation through a CsA-sensitive pathway. In addition, the results demonstrate that IL-2 alone is able to enhance thymocyte IL-2 responsiveness and IL-3 secretory responses in vitro. The ability of IL-2 to induce and maintain thymocyte function is discussed in the light of these results.
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PMID:Triggering of thymocyte function by IL-2 as the only exogenous stimulus; analysis of two distinct modes of IL-2-induced thymocyte proliferation and IL-3 secretion in vitro. 280 75

To understand molecular mechanisms of clonal expansion of lymphocytes we have isolated cDNA clones for two lymphokines, interleukins (IL) 4 and 5 that induce proliferation and maturation of B-lymphocytes. Structures of IL-4 and IL-5 revealed a remote homology with other lymphokines such as IL-3 and gamma-interferon. IL-4 and IL-5 were shown to affect not only B-lymphocytes but also T-lymphocytes and several other cells derived from bone marrow stem cells. We have also studied the structure and function of the IL-2 receptor: our focus was the molecular basis for the high and low affinity states of the receptor encoded by the identical cDNA. We propose the affinity conversion model that the high-affinity state of the IL-2 receptor is a ternary complex of IL-2, the IL-2 receptor, and a postulated "converter protein", which is fewer in number than the receptors.
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PMID:Growth factors and receptors of lymphocytes. 283 74


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