Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed cellular interactions between T lymphocytes and a recently established immortal glial line, L3 that retains several properties of immature oligodendrocytes (Aloisi et al., J Neurosci Res 27:16-24, 1990). L3 oligodendrocytes (L3-OL) cannot be induced to express class II antigens, nor do they specifically present antigen to syngeneic specific T lymphocyte. However, L3-OL strongly enhance the proliferation of freshly activated, interleukin-2(IL-2)-dependent T-line lymphocytes and concanavalin A (ConA)-activated lymphoblasts, irrespective of their antigen specificity or surface phenotype (CD4+ or CD8+). Resting and some activated T cells were susceptible to the mitogenic effect of L3-OL only in the presence of exogenous IL-2, not of other cytokines. The mitogenic effect of L3-OL did not depend on cell viability. It was observed in paraformaldehyde-fixed L3-OL cells and in membrane preparations, but not in culture supernatant. Neither intact L3-OL cells nor membrane preparations had direct IL-2 activity. The conclusion that the mitogenic effect of L3-OL cells is exerted by membrane structures acting as a costimulatory factor(s) of IL-2 is supported by the finding that it is largely blocked by a monoclonal anti-IL-2 receptor antibody. The effect is distinct from membrane-bound IL-1, membrane-bound tumor necrosis factor-alpha (TNF-alpha), IL-3, or IL-6 and cannot be reconstituted by these cytokines.
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PMID:Interaction between oligodendroglia and immune cells: mitogenic effect of an oligodendrocyte precursor cell line on syngeneic T lymphocytes. 138 59

FK506 is a recently introduced immunosuppressive agent synthesised by the microorganism Streptomyces tskubaensis. It has been found to be more potent than Cyclosporin A in inhibiting T cell activation. We investigated its effects on the expression of membrane bound as well as soluble interleukin-2 receptors on human lymphocytes. The membrane-bound IL-2 receptor expression was inhibited by FK506 in resting lymphocytes at a concentration of 1 pmol/l. At 10 nmol/l no further inhibition was seen. In activated lymphocytes FK506 exerted no inhibitory effect on the IL-2 receptor expression. The release of soluble IL-2 receptor showed a pronounced decline in the concentration interval between 10 pmol/l and 0.1 nmol/l. Above a concentration of 10 nmol/l, no further decrease was seen. In activated lymphocytes the expression of soluble IL-2 receptors was unaffected by FK506 incubated up to 72 h. Pretreatment of the lymphocytes with the compound did not further depress the expression of the membrane-bound or the soluble receptor. Our results also indicate that the expression of the membrane-bound receptor is more sensitive to the drug than the soluble form of the receptor.
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PMID:The immunosuppressive agent FK506 inhibits in vitro expression of membrane-bound and soluble interleukin-2 receptors on resting but not on activated human lymphocytes. 172 Apr 17

We studied the levels of membrane-bound and soluble-form interleukin 2 (IL-2) receptors in forty patients with rheumatoid arthritis. Levels of IL-2 receptors in the sera and synovial fluid of patients with rheumatoid arthritis were elevated when compared to values observed in normal sera and synovial fluid derived from the osteoarthritic joint. Simultaneous elevation of IL-2 receptor expression in blood and synovial fluid lymphoid cells was also detected, but no correlation was found between the two parameters nor between serum IL-2 receptor levels and the hemosedimentation rate. We conclude that measurement of serum concentrations of soluble IL-2 receptors should be used with caution as an index of disease activity, but may be useful when used in conjunction with other parameters in the management of patients with rheumatoid arthritis.
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PMID:Simultaneous evaluation of membrane bound and soluble interleukin 2 receptor expression in the blood and synovial fluid of patients with rheumatoid arthritis. 228 27

Interleukin 2 (IL-2) is a secreted glycoprotein which acts as an activation and proliferative signal for lymphocytes expressing membrane-bound glycoprotein IL-2 receptors. We have recently established that swainsonine (SW), an inhibitor of mannosidase II during N-linked glycoprotein processing, augmented mitogen-induced mononuclear leukocyte IL-2 receptor expression and IL-2-induced proliferation. The objective of the present investigation was to examine the effect of SW on lymphokine-activated killer (LAK) cell induction. Human mononuclear leukocytes were treated with various concentrations of SW (0.1-10 micrograms/ml) and IL-2 (1-100 units/ml) for up to 72 h. SW augmented IL-2-induced LAK activity directed against human lung carcinoma, melanoma, and leukemia cells 2-3-fold. LAK activity generated in the presence of SW at suboptimal doses of IL-2 (10 units/ml) was similar to that observed with higher concentrations of IL-2 (100 units/ml) alone. SW treatment alone or in combination with IL-2 increased the percentage of IL-2 receptor-positive cells. Furthermore, pretreatment with SW subsequently enhanced IL-2-induced lymphocyte proliferation. SW-treated mononuclear leukocytes exhibited an increase in high-mannose type glycoproteins based upon [3H]mannose labeling, susceptibility to alpha-mannosidase, and binding to concanavalin A-Sepharose. These results indicate that modulators of glycoprotein processing may be useful in lowering the concentrations of IL-2 required for LAK induction and maintenance.
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PMID:Potentiation of human lymphokine-activated killer cell activity by swainsonine, an inhibitor of glycoprotein processing. 250 Oct 20

We report a new, monocyte-independent system for the induction of activation and proliferation of human T cells in response to murine hybridomas expressing the OKT3 monoclonal antibody (OKT3 hybridomas). Incubation of nylon-wool-nonadherent (NA) lymphocytes or purified T cells with OKT3 hybridomas resulted in interleukin-2 (IL-2) production, expression of IL-2 receptor, modulation of the CD3 antigen, and proliferation. In contrast, murine hybridomas (OKT4, OKT8, anti-HLA-DR, and others) expressing monoclonal antibodies (mAb) other than OKT3 did not induce T-cell activation and proliferation. T cells did not respond to OKT3 mAb alone. OKT3 hybridomas alone did not produce interleukin-1 (IL-1) or other soluble factors that might be involved in the induction of IL-2 production by T cells, and they did not contain membrane-bound IL-1. In addition, IL-1 activity was not detected in cultures of NA-lymphocytes and OKT3 hybridomas, clearly demonstrating that IL-1 was not required, at least in this system, for T-cell activation and proliferation. Direct cell-cell contact between T cells and OKT3 hybridomas was required for IL-2 production. Thirty to fifty percent of T cells formed conjugates with the OKT3 hybridomas but not with the OKT4 or OKT8 hybridomas. Both conjugate formation and IL-2 production were significantly inhibited by the OKT3 mAb and by the anti-LFA-1 mAb. The cells responsible for IL-2 production were found to be of the T3+ T4+ T8- Leu 7- Leu 11- phenotype. IL-2 activity produced by NA-lymphocytes in response to OKT3 hybridomas became detectable as early as 1 hr and reached a maximum by 8 hr, preceding IL-2 receptor expression, modulation of the CD3 antigen, and [3H]thymidine incorporation of T cells. T cells produced higher concentrations of IL-2 in response to OKT3 hybridomas than in response to equal numbers of monocytes and OKT3 mAb. Addition of monocytes to cultures of T cells and OKT3 hybridomas resulted in suppression of IL-2 production in a concentration-dependent manner, suggesting that monocytes regulate the levels of IL-2 production. This monocyte-independent system may be useful for further dissection of T-cell activation and proliferation and its regulation by monocytes.
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PMID:Monocyte-independent interleukin-2 production and proliferation of human T cells in response to murine hybridomas expressing the OKT3 monoclonal antibody: interleukin-1 is not required for T-cell proliferation. 296 76

Activated T cells synthesize and express a cell membrane-bound receptor for interleukin-2 (IL-2) and have recently been shown to secrete a soluble form of the same receptor. Hairy cell leukemia is a chronic disorder caused by expansion of a clonal population of an unusual mononuclear cell of B cell origin. These cells have previously been shown to express an IL-2 receptor on the cell membrane. The sera of 26 patients with hairy cell leukemia were examined for the presence of a soluble IL-2 receptor before and during therapy with either recombinant interferon alpha-2a or 2'-deoxycoformycin. Before therapy, all patients had markedly elevated levels of this soluble IL-2 receptor ranging from five to 60 times the highest level observed in normal control sera. In individual patients changes in the level during therapy correlated well with clinical assessments of tumor response; levels fell to near the normal range in patients responding to therapy. Patients not responding to interferon alpha had no significant change in the soluble IL-2 receptor level. These results suggest that hairy cells secrete a soluble IL-2 receptor and that serial measurements of the level of this receptor in the serum can be used as a noninvasive means to assess disease response to therapy.
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PMID:Serum soluble IL-2 receptor as a tumor marker in patients with hairy cell leukemia. 312 46

One of the most central events during lymphocyte activation is the synthesis and release of IL-2. IL-2 induces the synthesis and expression of the IL-2 receptor alpha-chain (IL-2R) on the lymphocyte as well as the release of a truncated form of IL-2R (sIL-2R). The two proteins are identical except for the absence of the transmembrane and intracellular part on sIL-2R. We have in an in vitro model investigated the influence of certain compounds, affecting different parts of the proliferative response, on the release and expression of IL-2R. We found the generation of the two molecules to have different sensitivity to blocking of protein synthesis, glycosylation, microtubular assembly and proteolytic activity. However, blocking of intracellular transport from Golgi to the endoplasmic reticulum, disassembly of actin filaments and disturbances in the intracellular sodium/calcium balance had identical effects on expression and release of the respective IL-2R. These findings indicate a more complex and specific mechanism behind the generation of sIL-2R than simply by shedding through the action of proteases on the membrane-bound IL-2R.
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PMID:Influence of compounds affecting synthesis, modification and transport of proteins on the expression and release of interleukin-2 receptor. 753 4

The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.
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PMID:Membrane-bound and soluble IL-2 receptors (p55 and p75 chains) on peripheral blood mononuclear cells from patients with solid malignancies. 788 44

Vav has been shown to activate Ras (1-3) and is regulated by tyrosine phosphorylation (1) or binding of diglycerides (3) to the cysteine rich domain. In the present study employing different Ras activation assay techniques using [3H]GDP release or [32P]alpha GTP-binding from membrane-bound or soluble recombinant Ras, we demonstrate that Ras activity can be increased by tyrosine phosphorylated Vav upon cellular stimulation via the IL-2 receptor or the TCR/CD3-complex. Increase of [32P]alpha GTP-binding to Ras catalyzed by phosphorylated Vav is similar to the activity of immunoprecipitated Sos. The activity of Vav measured by binding of [32P]alpha GTP to Ras was linear with respect to the concentration of Vav protein used. To study molecular characteristics of this Vav-Ras interaction, we used several Ras mutants and demonstrate that Vav activity towards Ras depends on the integrity of the same or similar domains as Ras activation by SDC 25 or CDC 25.
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PMID:Molecular analysis of Ras activation by tyrosine phosphorylated Vav. 855 11

The recently cloned cytokine interleukin-15 (IL-15) shares several functional activities with IL-2 in different cell systems. Although IL-15 does not show sequence homology with IL-2, it uses components of the IL-2 receptor (IL-2R) for binding and signal transduction, namely, p75 (beta) and the p64 (gamma) chains of IL-2R. To evaluate whether IL-15 is involved in the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), we evaluated the ability of IL-15 to stimulate GL proliferation, cytotoxic function, and the role of IL-2R beta and gamma molecules on relevant cells. Our results show that IL-15 stimulates cell proliferation and cytotoxic activity of GL in LDGL patients. Reverse-transcriptase polymerase chain reaction (RT-PCR) and phenotypic analyses using the anti-IL-2R gamma-chain-specific TUGh4 monoclonal antibody (MoAb) indicate that both CD3+ and CD3- GL express the p64 IL-2R, a result previously unknown. IL-15 activity was inhibited by antibodies against p75 and p64 IL-2R chains, while no inhibitory effects are detectable with anti-p55 IL-2R antibody. The association of anti-p75 and anti-p64 IL-2R MoAbs resulted in a nearly complete (95%) inhibition of IL-15-induced GL proliferation. Using RT-PCR analysis, we demonstrated that highly purified CD3+ and CD3- GL did not express mRNA for IL-15 or IL-2. By contrast, a clear-cut IL-15 mRNA signal was detected by RT-PCR in patients' peripheral blood mononuclear cells, with monocytes likely accounting for the source of IL-15 in LDGL patients. However, even in concentrated supernatants from enriched monocyte populations, we could not demonstrate the presence of IL-15 protein. Using anti-IL-15 specific MoAbs, a membrane-bound form of this cytokine was demonstrated both on CD3+ and CD3- LDGL cells. By RT-PCR analysis, purified GL from these patients were found to express the message for IL-15 receptor alpha chain. Taken together, these results indicate that both CD3+ and CD3- GL are stimulated by IL-15 and that this cytokine mediates its activity through the beta and gamma chains of the IL-2R, providing further suggestions for the interpretation of the mechanisms that lead to cell expansion in patients with LDGL.
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PMID:Interleukin-15 triggers the proliferation and cytotoxicity of granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes. 897 93


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