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 (0.02 seconds)

An adenosine 3',5'-cyclic monophosphate (cAMP)-dependent growing cell line called CT-Mat was established by the long-term cultivation of an interleukin-2 (IL-2)-dependent human T-cell line, ILT-Mat, in the presence of cholera toxin instead of IL-2. CT-Mat cells can grow in the medium containing either cholera toxin or forskolin or cAMP derivatives. Although the CT-Mat cell line can still grow dependent on IL-2, the forskolin-induced growth of CT-Mat cells was demonstrated not to be mediated by an autocrine mechanism of IL-2 or any other growth factor. The intracellular cAMP level was elevated by treatment with the chemical agents but little by treatment with IL-2. These suggest that cAMP transduces intracellular growth signals different from those through the IL-2 receptor in an IL-2-dependent T-cell line CT-Mat.
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PMID:Establishment of a cyclic adenosine monophosphate-dependent growing human T-cell line derived from an interleukin-2-dependent cell line. 217 62

In view of the central involvement of interleukin-1 (IL-1) in T-cell functions and the negative effects exerted by cyclic adenosine monophosphate (cAMP) on T-cell responses, we wondered whether these inhibitions rely on defects in IL-1 generation. We investigated the effect of a known cAMP elevating agent, cholera toxin (CT), on the generation of IL-1 from peripheral blood adherent cells as well as the role of IL-1 whenever IL-2 synthesis and IL-2 receptor (CD25 antigen) expression are inhibited. While augmenting intracellular cAMP concentration, CT inhibits from 20 to 40% the generation of IL-1 activity from E. coli lipopolysaccharide (LPS)-stimulated adherent cells. Theophylline (TH), a cAMP degradation blocking agent, induces the same decrease in IL-1 activity. The B chain of CT, devoid of cAMP activating potency, is not inhibitory. In systems where CT and TH dramatically inhibit the generation of IL-2 activity (80%), addition of exogenous IL-1 does not restore the ability of T-cells to produce or release IL-2. Moreover, CT- and dibutyryl (db)cAMP-induced inhibition of CD25 antigen expression is not overcome by exogenous IL-1, IL-2, nor by both interleukins. It is concluded that inhibition of IL-1 and IL-2 production are independent and that inhibition of CD25 antigen expression is independent of IL-1 and IL-2 modulation. Cholera toxin and cAMP influences on interleukin synthesis are discussed.
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PMID:Elevation of cyclic adenosine monophosphate levels independently down regulates IL-1, IL-2, and IL-2 receptor (CD25) syntheses. 217 38

ADP ribosylation in the presence of cholera or pertussis toxin indicated the presence of G-proteins in Nb2 cell membranes. Two protein bands, with mol wt of 43.5K and 46.5K, were radiolabeled by cholera toxin, while a single protein (41.5K mol wt) was ADP ribosylated by pertussis toxin. Northern hybridization of total RNA from Nb2 cells with specific cDNA probes indicated the presence of mRNA transcripts encoding Gs, Gi2, Go, and, to a lesser extent, Gi3. A characteristic of receptors coupled to G-proteins is that their binding properties are regulated by guanine nucleotides. The binding of [125I]human GH to the lactogen receptor as well as the binding of [125I]IL-2 to the IL-2 receptor were decreased in a dose-dependent manner by GTP, GDP, and the analog guanosine 5'-O-(3-thiotriphosphate). GMP, however, had no effect. The addition of pyruvate kinase and phosphoenolpyruvate to regenerate GTP from GDP greatly increased the apparent potency of GTP. Cholera toxin inhibited PRL- and interleukin-2-stimulated DNA synthesis and cell proliferation in the Nb2 cells. In contrast, pertussis toxin had a differential effect on PRL- and IL-2-stimulated cells. Pertussis toxin, at an optimal concentration of 0.01 ng/ml, significantly enhanced the stimulatory effects of PRL on DNA synthesis (P less than or equal to 0.01; n = 9) and cell proliferation (P less than or equal to 0.05; n = 9) compared with the effect of PRL alone. However, at higher concentrations the toxin inhibited PRL-stimulated DNA synthesis and cell proliferation. Complete inhibition was achieved with 1000 ng/ml toxin. In contrast to the biphasic effect on PRL-stimulated cells, pertussis toxin was only weakly inhibitory to cells treated with IL-2. At the highest concentration tested, pertussis toxin (1000 ng/ml) inhibited IL-2-stimulated DNA synthesis and cell growth by only 30-35%. (Bu)2cAMP (IC50 = 0.019 mM) or methylxanthine (MIX; IC50 = 0.25 mM) also inhibited PRL-stimulated DNA synthesis. In the absence of mitogen, neither agent, from 0.0001-1 mM, had any effect on DNA synthesis. Similarly, IL-2-stimulated DNA synthesis in Nb2 cells was inhibited by (Bu)2cAMP (IC50 = 0.019 mM) or MIX (IC50 = 0.072 mM). However, MIX was approximately 3 times as potent in inhibiting the cell response to IL-2 as that to PRL. The susceptibility of Nb2 cells to both bacterial toxins suggests a role for G-proteins in regulating PRL- or IL-2-stimulated mitogenesis in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:G-proteins modulate prolactin- and interleukin-2-stimulated mitogenesis in rat Nb2 lymphoma cells. 246 72

Modulation of CD3 molecules and expression of receptors for IL-2 (CD25) are pivotal events of lymphocyte activation and proliferation. Knowing the inhibitory effect of cAMP elevating agents on T lymphocyte activation, we investigated the effect of cholera toxin (CT) and dibutyryl cyclic AMP (dbcAMP) on the modulation of the CD3/Ti complex and on the appearance of the CD25 antigen on PHA-activated human lymphocytes. Cytofluorometry analysis of indirectly anti-CD3 labelled cells showed that CT accelerated the disappearance of CD3 molecules and slowed their reappearance. CT or dbcAMP inhibited the expression of CD25 antigen. In both cases, not only the relative number of CD3+ or CD25+ cells decreased, but the number of CD3 or CD25 antigens per cell as well. Exogenous rIL-2 did not reverse the inhibition of IL-2R expression by CT, showing that this effect is independent of the inhibition of IL-2 production already demonstrated. We conclude that augmenting cAMP levels might affect early steps of activation such as antigen receptor modulation, but do affect more profoundly late IL-2 dependent steps especially the autocrine IL-2 pathway of IL-2 receptor upregulation and the production of IL-2.
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PMID:Elevation of 3'5' cyclic adenosine monophosphate alters CD3 and CD25 antigens expression in activated T lymphocytes. 256 Nov 59

In addition to the mobilization of neutrophils and monocytes, granulocyte-macrophage colony-stimulating factor (GM-CSF) also mobilizes lymphocytes into peripheral blood. We examined the ability of GM-CSF to induce the proliferation of purified human T cells (CD3+ CD4+ CD56- CD16- B1- MO2-) in two major aspects: (1) the mechanisms of GM-CSF interaction with interleukin-2 (IL-2) causing T-cell proliferation, and (2) the intracellular signals transmitted by GM-CSF in T lymphocytes. We observed that concentrations of GM-CSF between 0.01 ng/mL and 10 ng/mL had a synergistic effect with concentrations of IL-2 between 1 U/mL and 10 U/mL in stimulating T-cell proliferation. This effect of GM-CSF was maximal when it was added at the start of the culture. In situ hybridization showed the presence of mRNA for GM-CSF receptors in T cells. Further analysis showed that GM-CSF induced the expression of IL-2 receptor (IL-2R) on the surface of T lymphocytes. These events coincide with the ability of GM-CSF to increase the intracellular levels of both cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) in T cells, to increase the binding of (gamma-35S) GTP to T-cell membranes, and to enhance GTPase activity as determined by increased hydrolysis of 32P-GTP. IL-2 also induced IL-2R expression, cyclic nucleotide secretion, and G-protein activation. However, the presence of IL-2 reduced GM-CSF induction of these activities. Addition of antibodies to the alpha and beta subunits of IL-2R permitted the activation of G protein by GM-CSF even when IL-2 was present. Furthermore, GTP binding and GTPase activity induced by GM-CSF or IL-2 were inhibited by the addition of cholera toxin (CT), but not pertussis toxin (PT). Cumulatively, these results suggest that in T lymphocytes, receptors for GM-CSF or IL-2 may be coupled to the same CT-sensitive G protein, although other possibilities may exist. The role that G proteins play in mediating the intracellular signaling pathways induced by GM-CSF or IL-2 in human T cells is supported by adenosine diphosphate-ribosylation of a 44-kD or a 39-kD G protein in T-cell membranes by CT and PT, respectively.
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PMID:Priming effects of granulocyte-macrophage colony-stimulating factor are coupled to cholera toxin-sensitive guanine nucleotide binding protein in human T lymphocytes. 811 33

Anti-CD2 monoclonal antibody (mAb) can act synergistically with anti-CD3 to produce tolerance and diminish the anti-CD3-induced cytokine syndrome. Since interleukin(IL)-2 production and IL-2 receptor (IL-2R; CD25) expression are important determinants of CD3-driven T cell activation, the effects of anti-CD2 on anti-CD3-induced CD25 expression and IL-2 production were analyzed and related mechanistically to CD2-stimulated cAMP signaling with an in vitro model of T cell activation. The anti-CD2 mAb, 12-15, alone had no effect on splenic T cell CD25 expression and IL-2 production, while the anti-CD3 mAb, 145-2C11, caused significant increases in both CD25 expression and IL-2 production. The addition of anti-CD2 inhibited anti-CD3-induced increases in CD25 and IL-2. The inhibitory signal delivered by anti-CD2 was effective in many forms of T cell activation, since other stimuli which increased CD25, such as concanavalin A, phytohemagglutinin, and Staphylococcal enterotoxin B (SEB), could also be inhibited by anti-CD2. The inhibitory effect of anti-CD2 on CD25 could not be reversed by high doses of supplemental IL-2 added to the culture. Anti-CD2 increased cytoplasmic cAMP in a dose- and time-dependent manner. Reagents that increased cytoplasmic cAMP such as forskolin, cholera toxin, and 3'-isobutyl-1-methylxanthine could mimic the inhibitory effect of anti-CD2 on anti-CD3-driven CD25 expression. Anti-CD2 also increased the activity of cAMP-dependent protein kinase (PKA). H8, a PKA antagonist, blocked the inhibitory effect of anti-CD2 on CD25 expression, further confirming the role of PKA in CD2-induced negative signaling. The use of paired agonists to PKA demonstrated that a type I PKA was the preferential enzyme isoform stimulated by CD2 ligation. These findings show that increased cAMP and PKA activity mediate anti-CD2-induced suppression of anti-CD3-driven IL-2 production and CD25 expression, and provide mechanisms for anti-CD2-induced immunosuppression and inhibition of the cytokine syndrome associated with anti-CD3 treatment.
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PMID:Increased cAMP and cAMP-dependent protein kinase activity mediate anti-CD2 induced suppression of anti-CD3-driven interleukin-2 production and CD25 expression. 886 88

Activation and translocation of protein kinases C is a key event in the regulation of T lymphocyte activation, proliferation and function. Stimulation of human peripheral blood lymphocytes with the monoclonal antibody BMA 031 raised against the T cell antigen receptor led to a bimodal activation of protein kinases C. The immediate activation and translocation of the protein kinase C isoform PKC-alpha was followed by activation and translocation of the protein kinase C-beta isoenzyme after 90 min of stimulation. Pretreatment of the cells with cholera toxin for 90 min completely abolished activation of protein kinase C-alpha. In sharp contrast, activation and translocation of protein kinase C-beta was not influenced by the bacterial toxin, suggesting that activation and translocation of different protein kinase C isoenzymes are regulated by distinct mechanisms of transmembrane signalling coupled to the T cell antigen receptor/CD3 complex. The expression of high affinity IL-2 receptors was completely inhibited by cholera toxin, while IL-2 synthesis and secretion were not influenced in BMA 031-stimulated human lymphocytes. Extensive control experiments have shown that the effects of cholera toxin were not mediated by its B subunit, and were independent of elevation of intracellular cAMP concentration, suggesting that cholera toxin interfered with a signalling pathway leading to activation of protein kinase C-alpha, which could be responsible for the inhibition of IL-2 receptor expression. This hypothesis was substantiated by the finding that upon introduction of antibodies against protein kinase C-alpha, IL-2 receptor gene expression was completely suppressed. The results suggest, that protein kinase C-alpha might be the major protein kinase C isoenzyme of a signal transduction cascade regulating IL-2 receptor expression in stimulated human lymphocytes.
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PMID:T cell antigen receptor dependent signalling in human lymphocytes: cholera toxin inhibits interleukin-2 receptor expression but not interleukin-2 synthesis by preventing activation of a protein kinase C isotype, PKC-alpha. 915 Feb 81

We have studied how cholera toxin (CT) and its non-toxic cell-binding B-subunit (CTB) affect the activation of pure human T cells in an anti-CD3-driven system. CT, as opposed to CTB, strongly suppressed the proliferative responses as well as cytokine production in CD4+ and CD8+ T cells. CT however, had a differential effect on naive and activated/memory T cell subsets. Costimulation through exogenous IL-2 or through CD28 cross-linking rescued the proliferation of CT-treated naive CD45RA+ T cells, but not of activated/memory CD45RO+ cells. IL-2 production and IL-2 receptor expression were markedly reduced by CT in all T cell fractions, i.e. also in CD45RA+ cells which had maintained proliferative responses. However, the proliferative responses of CT-treated CD45RA+ T cells were IL-2-dependent, as shown by blocking experiments using anti-IL-2 antibodies. These results indicate (i) that CTB has no cytostatic effect on human T cells, (ii) that CT affects proliferation and cytokine production by two different signal pathways, and (iii) that CT might interact with a signal pathway generated through or influenced by CD45.
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PMID:Differential effect of cholera toxin on CD45RA+ and CD45RO+ T cells: specific inhibition of cytokine production but not proliferation of human naive T cells. 1093 Nov 43

Various vaccine adjuvant candidates were assessed with the modified-live porcine reproductive and respiratory syndrome virus (MLV PRRSV) (Ingelvac PRRS MLV) vaccine. Their influence on humoral-mediated immune (HMI) and cell-mediated immune (CMI) responses as well as protection from virulent PRRSV challenge (MN-184) was evaluated. Ninety seronegative pigs were randomly divided into nine groups of 10 pigs. One group received MLV vaccine alone. Five groups received MLV vaccine with either bacterial endotoxin-derived adjuvant (ET), mixed open reading frame 5 (ORF5) peptides derived from various PRRSV isolates, porcine interferon alpha (IFNalpha), polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC), or porcine interleukin-12 (IL-12). One group did not receive MLV vaccine but was immunized with ORF5 peptides conjugated with cholera toxin (ORF5 peptide/CT). Two groups served as challenged and unchallenged non-vaccinated controls. Four-color flow cytometry was utilized to simultaneously identify three major porcine T-cell surface markers (CD4, CD8, and gammadelta TCR) and detect activation marker CD25 (alpha chain of IL-2 receptor) or intracellular IFNgamma. The MLV PRRSV vaccine alone successfully primed CD4(-)CD8(+)gammadelta- T-cells as demonstrated by a significant increase in %IFNgamma+ cells when live PRRSV was used as a recall antigen. Booster immunizations of mixed ORF5 peptides and co-administration of IL-12 with MLV PRRSV vaccine significantly enhanced IFNgamma expression by some T-cell subsets (CD4(-)CD8(+)gammadelta+ and CD4(-)CD8(-)gammadelta+ for mixed ORF5 peptides and CD4(+)CD8(+)gammadelta- and CD4(-)CD8(+)gammadelta+ for IL-12). All groups receiving MLV-vaccine with or without adjuvants had reduced lung lesions after challenge. The group immunized with only ORF5 peptide/CT did not have significant T-cell recall responses and was not protected from challenge. Expression of IFNgamma by several T-cell subsets correlated with reduced lung lesions and viremia, whereas expression of CD25 did not. Expression of surface CD25 did not correlate with IFNgamma production. PRRSV ELISA s/p ratio prior to challenge also correlated with reduced lung lesions and viremia. In conclusion, booster immunizations of the mixed ORF5 peptides and co-administration of IL-12 effectively enhanced the CMI response to MLV vaccine. However, neither adjuvant significantly contributed to reducing clinical effects when compared to MLV alone.
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PMID:Immune responses and protection by vaccine and various vaccine adjuvant candidates to virulent porcine reproductive and respiratory syndrome virus. 1616 19