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

The effects of syncytiotrophoblast plasma membrane vesicles (STPM) on stimulated Jurkat leukemic T cells have been investigated. STPM inhibited IL-2 production and the expression of protein P55 of the IL-2 receptor (IL-2R P55), when Jurkat cells were stimulated by a combination of calcium ionophore A23187 (CaI) + phorbol 12-myristate 13-acetate (PMA). STPM also inhibited IL-2R P55 when cells were stimulated by PMA alone, a situation in which IL-2 production is negligible. On the other hand, STPM had no effect on the sustained mobilization of intracellular Ca2+ induced by CaI nor on the PKC-dependent CD3 down regulation induced by PMA. Finally STPM had no effect on intracellular cAMP levels. These results show that (i) the inhibitory effect of STPM on IL-2R P55 expression is independent of the inhibition of IL-2 production, and (ii) the inhibitory effects of STPM are at least partially independent of phosphatidylinositol 4,5-bisphosphate hydrolysis. They suggest that STPM affect a signaling pathway activated by PMA but possibly PKC independent.
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PMID:Inhibitory effect of human syncytiotrophoblast plasma membrane vesicles on Jurkat cells activated by phorbol ester and calcium ionophore. 130 91

Adherent cells from HIV-infected subjects as well as in vitro HIV-infected normal adherent cells produce spontaneously a 29-kD (p29) factor that inhibits mitogen-induced proliferation of normal T cells. p29 mediates a partial dose-dependent inhibition of total protein synthesis in both nonstimulated and PHA-activated cells that is associated with impaired PHA-induced expression of IL-2 receptor (IL-2R)alpha chain, HLA-class II molecules, and production of IL-2 by these cells; conversely, p29 does not modify the expression of IL-2R beta chain, 4F2, CD9, or transferrin receptor, or the production of IL-1 and TNF alpha by the cells. 1 h preincubation of the cells with p29 is sufficient to detect its biologic activity and added rIL-2 abrogates p29-induced inhibition of IL-2R alpha chain expression; however, p29 does not display any biologic effect on already expressed IL-2R alpha chains. The impaired expression of IL-2R alpha chain mediated by p29 is not due to a decreased accumulation of the corresponding mRNA transcripts, but is associated with a two-fold increase of intracellular cAMP. Binding experiments with 125I-rIL-2 reveals that p29 induces a 50% decrease in the number of both high and low affinity IL-2R per cell. p29 also inhibits alloantigen-induced proliferation of PBMC, whereas it does not modify IL-2-dependent proliferation of 48-h PHA-blasts that already express high affinity IL-2R. These findings indicate that p29 mediates its biologic activity during early stages of T cell activation affecting the expression of high affinity IL-2R and production of IL-2, through a nontranscriptional mechanism involving an increase of intracellular cAMP.
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PMID:Human immunodeficiency virus-infected adherent cell-derived inhibitory factor (p29) inhibits normal T cell proliferation through decreased expression of high affinity interleukin-2 receptors and production of interleukin-2. 132 45

The primary IgM response of murine B lymphocytes against red blood cell-bound antigens can be induced by incubating antigen-reactive B cells either with the lymphokines interleukin-1 (IL-1) and IL-2 together with the nucleoside cAMP, or by the addition of antigen-specific helper T cells. The reactivity of B cells is strongly influenced by the T-cell lymphokine IL-2. IL-2 inhibits the cyclic adenosine 3',5'-phosphate (cAMP)-dependent B-cell response when it is allowed to act on the cells prior to cAMP. On the other hand, if IL-2 acts on B cells together with or after cAMP, it synergizes with the nucleoside and enhances the immune response. A similar effect of IL-2 is observed in the T-cell-mediated activation of B cells. If IL-2 is present before helper T cells interacted with B cells, it inhibits antibody production. The inhibitory IL-2 effect is reversed by the simultaneous addition of exogenous cAMP. The finding supports the hypothesis that Ia ligation by T cells results in B cells in the elevation of cAMP which acts as an important second messenger in B cells. The antagonism between cAMP and IL-2 was also examined in the pre-B-cell line 70Z/3. The nucleoside is highly toxic to 70Z/3 pre-B cells and a majority disintegrates within hours of exposure to the nucleoside. The surviving cells undergo phenotypic differentiation expressing surface Ig kappa chains and major histocompatibility complex (MHC) class II molecules, and increase the expression of IL-2 receptor (R). The phenotypic differentiation requires the presence of IL-1. IL-2 inhibits both of these B-cell responses to cAMP, the IL-1-independent cell death, and the IL-1-dependent phenotypic differentiation.
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PMID:Interleukin-2 may enhance or inhibit antibody production by B cells depending on intracellular cAMP concentrations. 133 Aug 97

Using purified human T lymphocytes stimulated in serum-free media with adhered anti-CD3 + exogenous IL-2, we have shown that elevated [cAMP]i (mimicked by CPT-cAMP or induced by the physiological agonist PGE2) directly inhibits mitogen-induced 1) [3H]thymidine incorporation by PBMC, purified T cells, and isolated CD4+ and CD8+ T cell subpopulations; 2) expression of both high- and low-affinity IL-2 receptors; 3) plasma membrane expression of both p55 and p75 subunits of the IL-2 receptor; and 4) expression of p55 mRNA, but not p75 mRNA. The decrease in p55 mRNA is not due to enhanced mRNA metabolism. We conclude that elevated [cAMP]i, acting directly on T cells, inhibits mitogenesis by decreasing IL-2 receptor expression. We discuss the possible physiological relevance for the multiple stages of T cell activation that are sensitive to elevated [cAMP]i.
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PMID:Cyclic AMP directly inhibits IL-2 receptor expression in human T cells: expression of both p55 and p75 subunits is affected. 184 80

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

The cell-surface receptor for interleukin-2 (IL-2) consists of two unlinked polypeptides of 55 and 75 kDa (p55, p75). The monoclonal antibody antiTac binds to p55 alone. We show here that the binding of either IL-2 or antiTac to the surface of T lymphocytes triggered the generation of cAMP. Reagents which activate adenyl cyclase by stimulation of its guanine nucleotide-binding protein (Gs) also stimulated increases in cAMP. All of the above reagents, and cAMP itself, stimulated the turnover of phosphate residues bound to serine and threonine residues of an 85 kDa protein. The data provide evidence that the binding of ligands to the p55 component of the IL-2 receptor generates a biochemical signal by the stimulation of adenyl cyclase via Gs, and that the consequent generation of cAMP and activation of cAMP-dependent protein kinase modulates the turnover of p85-bound phosphate groups.
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PMID:The binding of ligands to the 55 kDa component of the interleukin-2 receptor triggers increased turnover of phosphate bound to an 85 kDa protein. Evidence for the role of cyclic AMP. 253 32

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

The mechanism by which purinergic agonists modulate murine T-lymphocyte activation and proliferation was investigated. Adenosine and other compounds such as ATP and 2-chloroadenosine (ClAdo) were found to block T-cell mitogenesis induced by concanavalin A (Con A) in a dose-dependent fashion. The nonmetabolizable adenosine analog ClAdo was the most potent agent capable of inhibiting T-cell mitogenesis. Extracellular addition of the permeable cAMP analog dibutyryl cyclic AMP (dbcAMP) also led to a dose-dependent blockade of T-cell mitogenesis, although with less efficiency when compared to ClAdo. Addition of IL-2-enriched fluids failed to reverse blockade of T-cell mitogenesis by ClAdo or dbcAMP. ClAdo blocked T-cell enlargement induced after 20 hr of culture with Con A. We analyzed the effect of micromolar concentrations of ClAdo on interleukin-2 (IL-2) production, expression of IL-2 receptors (7D4 and 3C7 surface antigens), and induction of IL-2 responsiveness after in vitro cultivation with Con A. ClAdo inhibited both IL-2 secretion and induction of IL-2 responsiveness up to control levels in the same dose range it inhibited T-cell mitogenesis. However, cell surface expression of IL-2 receptors was not affected. Short incubations of resting splenic T cells with ClAdo led to a dose-dependent accumulation of cyclic AMP in responding cells. This effect was markedly reduced by the purinergic antagonist 3-isobutyl-1-methylxanthine (IBMX) but was not prevented by the adenosine uptake blocker dipyridamole. ClAdo elicited cAMP accumulation in the same dose range it inhibited T-cell activation events. Extracellular administration of dbcAMP to splenic T cells stimulated by Con A mimicked the effects of ClAdo on T-cell activation parameters, as revealed by a dose-dependent blockade of both IL-2 secretion and IL-2 responsiveness induction, without affecting IL-2 receptor expression. Short incubations of Con A-activated T-cell blasts with ClAdo also led to a dose-dependent accumulation of cAMP. We then analyzed the effect of purines and dbcAMP on IL-2-mediated activated T-cell growth. Purines caused a dose-dependent inhibition of IL-2-mediated T-cell proliferation and ClAdo was the most potent purinergic agonist tested. The effect of ClAdo on Con A-induced T blasts was shifted to the right, if compared to earlier T-cell activation steps.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Purinergic modulation of T-lymphocyte activation: differential susceptibility of distinct activation steps and correlation with intracellular 3',5'-cyclic adenosine monophosphate accumulation. 301 70

1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a protein kinase inhibitor, suppressed interleukin 2 (IL-2) production and IL-2 receptor (IL-2R) expression of the human leukemic T-cell line, Jurkat, induced by 12-O-tetradecanoyl-phorbol-13-acetate and phytohemagglutinin-P. This effect was significant at 5 microM H-7 without loss of cell viability. Such activity was not observed with N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), a potent inhibitor of cGMP- and cAMP-dependent kinases, and a weak inhibitor of Ca2+-phospholipid-dependent protein kinase (protein kinase C). These findings suggest that protein kinase C is more closely associated with IL-2 receptor expression and IL-2 production of T cells than cGMP- or cAMP-dependent kinases. In addition, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor, suppressed both IL-2 production and IL-2R expression. Cycrosporin A (Cy A), a potent immunosuppressive drug, markedly inhibited IL-2 production of Jurkat cells whereas it did not affect the IL-2R expression. Thus, the mechanism of action of Cy A appears to differ from that of the protein kinase inhibitor, H-7, and the calmodulin inhibitor, W-7.
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PMID:Inhibitors of IL-2 production and IL-2 receptor expression in human leukemic T-cell line, Jurkat. 310 62

The ileal Peyer's patch (PP) plays a central role in B cell development in young sheep and it is hypothesized that this B cell development occurs independent of extrinsic antigen and T cells. Therefore, it was of interest to examine ileal PP follicular (iPf) B cell responses to CD40 ligand, a molecule integral to T cell-dependent B cell development. A variable level of CD40 expression was detected on a subpopulation of iPfB cells and J558L cells, expressing a membrane form of mouse CD40 ligand (mCD40L), interacted specifically with the CD40 molecule on iPfB cells. In response to mCD40L the non-S phase iPfB cells were rescued from apoptotic cell death and there was a marked proliferative response but viable cell number remained relatively constant. The mCD40L also induced decreased cytoplasmic cAMP levels, blocked anti-Ig-induced iPfB cell death and induced functional IL-2 receptor expression on a subpopulation of iPfB cells. Many of the mCD40L-induced responses of iPfB cells were similar to those reported for germinal centre and immature B cells, and indicated that cognate T cell-B cell interaction could influence iPfB cell proliferation and differentiation. Finally, that mCD40L induced iPfB cell activation and differentiation was evident as increased expression of CD5, the BAQ44A molecule, the CACT65A molecule and the expansion of surface IgG1+ B cells. These mCD40L-induced phenotypic changes were also observed on subpopulations of freshly isolated iPfB cells and jejunal PP follicular B cells. However, few iPfB cells had a phenotype similar to that observed in co-culture with mCD40L and this suggested that T cell-dependent B cell development may play a minor role in ileal PP B cell development. The possible significance of CD40 signalling is discussed in terms of the selection of iPfB cells during development.
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PMID:CD40 signalling in ileal Peyer's patch B cells: implications for T cell-dependent antigen selection. 754 Aug 60


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