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)

There are presently no monitoring tools to assess the immunosuppressive effect of cyclosporine (CsA) in vivo, since the mode of drug action is incompletely understood in man. Experimental in vitro studies suggest that CsA causes reversible inhibition of T helper cell generation of interleukin-2 (IL-2). Therefore the present study examined the effect of CsA administered in vivo on the capacity of kidney transplant recipient lymphocytes to generate IL-2 after mitogen (phytohemagglutinin [PHA]) stimulation. IL-2 production was measured by the capacity of lymphocyte supernates to trigger proliferation of a human IL-2-dependent T cell line. Peripheral blood lymphocytes (PBL) from CsA-Pred treated recipients displayed 40.6% inhibition (1.14 +/- 0.06 U/ml, n = 117, P less than 0.001) of IL-2 production compared with normal individuals (1.93 +/- 0.04 U/ml, n = 164). Dialysis patients did not display inhibited IL-2 production. The inhibition of IL-2 generation was observed in patients treated solely with CsA without supplemental corticosteroids (1.24 +/- 0.12 U/ml, n = 25; 35.8% inhibition, P less than 0.001). CsA did not inhibit the expression of the IL-2 receptor: 4.15 +/- 11.2% and 63.1 +/- 10.3 of normal lymphocytes and 36.7 +/- 9.8% and 60.4 +/- 12.2% of CsA-treated patient lymphocytes expressed anti-IL-2 receptors after 24 or 48 hr of PHA stimulation, respectively. Serial posttransplant studies in individual patients confirmed no inhibition of IL-2 generation pretransplant (1.94 +/- 0.07 U/ml) followed by a high degree of inhibition thereafter, namely 0.87 U/ml (55.0% inhibition) at 1 week, 1.15 U/ml (40.6% inhibition) at 2 weeks, 0.42 U/ml (78.2% inhibition) at 3 weeks, and 0.99 U/ml (48.7% inhibition) at 4 weeks. There was a correlation between the occurrence of rejection episodes in the 7 patients who suffered this event, and IL-2 generation by patient PBL. Before pulse therapy there was no inhibition of IL-2 generation (2.39 U/ml; -23.8 inhibition), documenting a poor level of immunosuppression in these patients. At 1, 2, 3, or 4 days after corticosteroid pulse therapy, PBL displayed 39.4%, 57.0%, 50.0% and 49.2% inhibition, respectively. These findings suggest not only that CsA treatment impairs the generation of IL-2 by patient lymphocytes, but also that failure to display this response is associated with a poor level of immunosuppression and allograft rejection. These studies provide a foundation for serial analyses of IL-2 generation, in order to dissect its utility as a pharmacodynamic parameter to assess the level of CsA-induced immunosuppression.
Transplantation 1985 Dec
PMID:Pharmacodynamic assessment of the in vivo cyclosporine effect on interleukin-2 production by lymphocytes in kidney transplant recipients. 393 6

During immune response to an allograft, activated T cells express a number of cell surface activation antigens, among them the membrane receptor for the lymphokine interleukin 2 (IL-2). As the IL-2 receptor is not present on resting T cells, it offers an attractive target for potentially specific immunosuppressive therapy. The rat monoclonal antibody M7/20, which binds to the murine IL-2 receptor, was studied for its effect on allograft survival in two H-2-incompatible strain combinations in inbred mice. Treatment with M7/20 for 10 days markedly prolonged survival of vascularized, heterotopic heart allografts in both strain combinations, with indefinite graft survival in 50% of recipients. The same treatment significantly prolonged skin allograft survival in one of the two combinations. The results support the important role of the IL-2 receptor in the mechanism of graft rejection and confirm its suitability as a target for immunosuppressive therapy in transplantation.
Transplantation 1985 Dec
PMID:The effect of anti-interleukin-2 receptor monoclonal antibody on allograft rejection. 393 7

We show that purified recombinant interleukin 2 (rIL-2) alone induces the expression of high- and low-affinity interleukin 2 (IL-2) receptors in vitro on human T cells and thymocytes that have not been activated previously by lectins or other inducing agents. IL-2 receptors are expressed after 24 hr, as determined by the binding of 125I-labeled monoclonal anti-IL-2 receptor antibody 2A3, which binds equally to high- and low-affinity receptors. High-affinity receptors were distinguished from low-affinity receptors by the binding of 125I-labeled IL-2 to T cells and by the proliferative response of thymocytes to IL-2, in concentrations that selectively interact with the high-affinity class of IL-2 receptors. The IL-2-induced proliferation of thymocytes in vitro induced by IL-2 alone is dependent upon the concentration of IL-2 and is inhibited by monoclonal anti-Tac antibody, indicating that the proliferative response is mediated by the binding of IL-2 to the receptors. In addition, we demonstrate that IL-2 augments the number of high-affinity receptors on concanavalin A-activated thymocytes. These results document that IL-2 acts as a hormone that induces the activation of thymocytes and T cells, as evidenced by the de novo induction of biologically active, high-affinity IL-2 receptors. IL-2 also upregulates the expression of high-affinity IL-2 receptors on activated thymocytes. These observations illustrate the biologic importance of the regulatory role of IL-2 in the immune response.
Proc Natl Acad Sci U S A 1985 Dec
PMID:Induction and upregulation by interleukin 2 of high-affinity interleukin 2 receptors on thymocytes and T cells. 393 41

A new method for the determination of both low and high affinity binding sites on interleukin 2 (IL-2) target cells is described, which is based on differential dissociation of the ligand receptor complex. The technique requires highly purified but not radiolabelled IL-2. In the presence of activated charcoal the low affinity binding sites had a dissociation half time of less than 1 min, while that of the high affinity binding sites was 80 min. Human T-lymphocytes expressed both classes of binding sites within 48 h after PHA stimulation. During culture of PHA-stimulated T-lymphocytes, low affinity binding sites appeared on day 2 and remained high until day 8. High affinity binding sites appeared on day 1, were highest on day 2, and remained high until day 6. The changes in the concentration of the high affinity binding sites are considered as being the result of: receptor stimulation by PHA and/or IL-2 (days 1-2); receptor down regulation by extensive IL-2 production (day 3); increase of unoccupied IL-2 receptor after disappearance of IL-2 from the medium (days 4-6) and cessation of receptor synthesis and receptor breakdown (days 7-10).
Clin Exp Immunol 1985 Dec
PMID:Binding of interleukin 2 to target cells: determination of high and low affinity binding sites on T-lymphoblasts by differential dissociation. 393 57

In the present study the activation of purified human T lymphocytes by the calcium ionophore A23187 was analysed in the light of current concepts of receptor-linked inositol lipid metabolism. It was found that A23187 was only slightly mitogenic, with a narrow optimum at 400-500 nM. The proliferation could be blocked by anti-Tac ascites at 10(-3) dilution, suggesting an interleukin 2 (IL-2)-dependent pathway of activation. However, an unexpectedly large proportion of A23187-stimulated cells expressed the IL-2 receptor. Reculturing the cells with exogenous IL-2 after removal of A23187 resulted in strongly enhanced proliferation. Phorbol myristic acetate (PMA) at non-mitogenic concentrations exerted an extremely strong synergistic effect on A23187-induced cell proliferation, which was, again, mediated via an IL-2-dependent pathway. Supernatants of A23187-stimulated T cells did not contain detectable amounts of IL-2. Combination of PMA and A23187 resulted in considerable IL-2 production. It is concluded that A23187 induces the expression of IL-2 receptors without concurrent stimulation of IL-2 production, thus allowing only low levels of proliferation. Addition of exogenous IL-2 or of PMA restores the imbalance between the occurrence of IL-2 and its receptor and results in high rates of proliferation.
Scand J Immunol 1985 Dec
PMID:Calcium ionophore A23187 induces interleukin 2 reactivity in human T cells. 393 26

We have previously reported the isolation of 2 human allospecific cytotoxic T-lymphocyte (CTL) clones that can undergo a reversible functional change from a highly lytic phase to a nonlytic quiescent phase and again to a lytic phase. The entire process was found to be regulated by recombinant interleukin 2 (rIL-2). We have now extended these studies in 3 ways. First, we show that specific alloantigens can also function as a signal to reactivate lytic function in the reverted CTL. However, in contrast to CTL reactivated with rIL-2, the antigen-reactivated CTL apparently fail to undergo subsequent cell division. Second, we have also found that this reversion phenomenon is not the same for all CTL tested, as 2 other CTL clones were found that did not revert to the non-lytic phase when cultured for up to 60 h in rIL-2-free medium. Third, the expression of Tac (IL-2 receptor) was also studied throughout the process of reversion and reactivation. rIL-2 added to the cell that had reverted to a non-lytic phase induced, an increase in the expression of Tac receptors during the reactivation phase, to levels greater than those expressed on cells continuously cultured in rIL-2-supplemented medium.
Scand J Immunol 1985 Dec
PMID:Loss and re-acquisition of lytic function by cloned cytotoxic T lymphocytes: role of specific antigen and interleukin 2. 393 29

Human peripheral blood lymphocytes cultured for 4 days in the interleukin 2 (IL-2)-containing cell-free supernatant of the MLA144 cell line (MLA144CM) are cytolytic to NK-susceptible and NK-resistant tumor target cells. This lymphokine-activated killer (LAK) activity is dependent on IL-2 as development of LAK activity is inhibited in the presence of a monoclonal antibody (MoAb) reacting with the IL-2 receptor (anti-Tac). Addition of cyclosporin A (CyA) to mixed lymphocyte cultures inhibits the development of allospecific cytotoxic activity and inhibits the development of IL-2 responsiveness. However, development of LAK activity is unaffected by the inclusion of CyA in the cultures, showing that the LAK precursor can be functionally distinguished from the allospecific cytotoxic precursor cell. Development of LAK activity does not require mature NK cells as shown by the generation of LAK activity from NK inactive human thymocytes and lymph node cells. In addition, depletion of NK activity from human PBL does not impair the development of LAK activity.
Cell Immunol 1985 Dec
PMID:Functional studies on the precursors of human lymphokine-activated killer cells. 393 93

B cells cultured with anti-IgM, BSF-p1, and B15-TRF will differentiate into high rate IgM-synthesizing cells in the presence of supernatants from EL-4 cells that have been induced with phorbol myristate acetate. These supernatants contain two molecular species (EL-TRFs) that have differentiative activity. One co-migrates with interleukin 2 (IL-2) and its activity is blocked by antibody to the IL-2 receptor. Furthermore, molecularly cloned IL-2, at concentrations of 100 U/ml or more, expresses such EL-TRF activity. The EL-TRF activity of cloned IL-2 can also be inhibited by antibody to the IL-2 receptor. The other material with EL-TRF activity has a molecular weight of approximately 32,000. This material lacks IL-2 activity. Antibody to the IL-2 receptor does not impair its function. B cells stimulated with anti-IgM and BSF-p1, with or without B15-TRF, express determinants that react with two monoclonal antibodies which recognize distinct epitopes on the T cell IL-2 receptor. These determinants are present at much lower density (approximately 100-fold) on stimulated B cells that on HT-2 cells, an IL-2-dependent T cell line. Very small amounts of [3H]IL-2 (less than 1,000 molecules per cell) bind to activated B cells. These results indicate that IL-2 binds to a receptor on appropriately prepared B cells and causes them to differentiate into high rate IgM-synthesizing cells. The physiologic significance of the B cell differentiative activity of IL-2 remains to be investigated.
J Exp Med 1984 Dec 01
PMID:Both interleukin 2 and a second T cell-derived factor in EL-4 supernatant have activity as differentiation factors in IgM synthesis. 643 14

There is increasing evidence suggesting that the monoclonal antibodies ART-18, AMT-13 and anti-Tac recognize species-specific antigenic determinants of the interleukin-2 (IL-2) receptors of rat, mouse and human origin, respectively. In order to compare directly the molecules (glycoproteins) recognized by these antibodies, concanavalin A (ConA) activated T-lymphocytes of the respective species were surface labeled with 125I, after which the materials immunoprecipitated by the appropriate anti-IL-2 receptor antibodies were subjected to SDS-PAGE analysis. The noncross-reacting antibodies ART-18 and AMT-13 both precipitated a 50-55-kD molecule. The anti-Tac-reactive material (the putative human IL-2 receptor) is considerably different (60-65 kD) from those precipitated by antibodies ART-18 and AMT-13 (the putative rat and mouse IL-2 receptors). An indirect binding assay using the anti-mouse IL-2 receptor antibody AMT-13 showed that, after addition of ConA to spleen cell cultures, T-lymphocytes expressed IL-2 receptors before the onset of the ConA-induced DNA synthesis. The ConA-induced expression of the IL-2 receptor is apparently a transient event. IL-2 receptor bearing cells progressively lost their receptors (within 6 days) when recultured in the absence of ConA. Cells re-exposed to ConA regained IL-2 receptors. Short exposure of T-cells (thymocytes) to ConA or the nonmitogenic compound phorbol myristate acetate (PMA) is not sufficient to trigger IL-2 receptor expression. Murine thymocytes incubated with PMA for 30 min or with ConA for 4 hr (mitogen-pulsed T-cells) failed to bind the anti-IL-2 receptor antibody AMT-13 and to absorb IL-2 activity present in semipurified IL-2 preparations, but they proliferated vigorously in response to the same IL-2 preparations. The IL-2 preparations, when absorbed with thymocytes, lost: (1) the capacity to generate IL-2 receptors, and (2) the capacity to induce proliferation of mitogen-pulsed cells; but they retained the capacity to induce proliferation of T-lymphoblasts. These results suggest the existence of a factor, IL-2 receptor inducing factor (RIF), present in the IL-2 preparations. It is postulated that RIF is a prerequisite for the acquisition of IL-2 receptors and consequently for IL-2 responsiveness by lectin-activated cells.
Mol Immunol 1984 Dec
PMID:Studies on the interleukin-2 receptor, its generation and dynamics using monoclonal anti-interleukin-2 receptor antibodies. 644 Nov 15

We have established non-lymphoid cell lines HeLa, Ltk and NIH3T3 expressing the human interleukin-2 (IL-2) receptor by transfection of human IL-2 receptor complementary DNA. While IL-2 receptors on T cells are classified into the high and low affinity species, the receptors expressed on the cDNA-transfected non-lymphoid cells belong to the low affinity species. These IL-2 receptors could not transmit the growth signal although they were similar in size to those expressed on T cells. Phorbol ester-induced phosphorylation of the IL-2 receptors on HeLa cells did not affect the affinity of the receptor. We have also constructed a cDNA encoding a mutant IL-2 receptor that replaced the major phosphorylation site, the serine residue at position 247 with the glycine residue. This mutant IL-2 receptor expressed on non-lymphoid cells also had the low affinity for IL-2. The results indicate that the high and low affinity states of the IL-2 receptor are not solely determined by phosphorylation of the receptor. The IL-2 receptors expressed on these non-lymphoid cells were internalized four to eight times more slowly than those on T cells. Possible defects of the IL-2 receptors expressed on non-lymphoid cells are discussed.
Mol Biol Med 1984 Dec
PMID:Properties of human interleukin-2 receptors expressed on non-lymphoid cells by cDNA transfection. 644 99


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