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)

Total lymphoid irradiation is an effective immunosuppressive therapy used to prepare patients for organ transplantation and to treat several autoimmune diseases. We have used the mouse model to investigate the mechanism of TLI-induced immunosuppression. Mice were irradiated with 250-rad daily fractions to a total dose of 3500 rads. Splenocytes from control and TLI-treated mice were analyzed for IL-2 production, IL-2 receptor expression after mitogen stimulation, and percent L3T4 positive cells. At two weeks following the completion of TLI, IL-2 production from whole spleen populations had decreased 90% compared with controls (TLI mean IL-2 units = 25 +/- 9.0, control mean = 277 +/- 104). IL-2 receptor expression on splenocytes following Con A stimulation was decreased 80% compared with controls (TLI mean percentage of IL-2 receptor expressing cells = 16.2 +/- 4.1, control mean = 82.0 +/- 7.5). L3T4+ cells that expressed IL-2 receptor were also decreased following TLI (TLI mean = 4.4 +/- 1.4, control mean = 22.0 +/- 3.8), as were proliferative responses to Con A and PHA. Addition of recombinant mouse IL-2 did not restore IL-2 receptor expression or proliferative responses. Whole TLI-treated splenocytes did not suppress IL-2 production or proliferative responses of normal splenocytes. These immunologic abnormalities recovered over time, and by 8 weeks post TLI IL-2 production, IL-2 receptor expression, L3T4+ cell numbers and proliferative responses had returned toward normal. These results suggest that TLI therapy transiently depletes IL-2 producing, IL-2 receptor expressing, and mitogen responsive lymphocytes. The immunosuppression is not mediated through a suppressor cell and is independent of IL-2 production.
Transplantation 1989 Sep
PMID:The immunosuppressive mechanism of total lymphoid irradiation. I. The effect on IL-2 production and IL-2 receptor expression. 257 Dec 7

The effect of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25(OH)2D3) on the expression of interleukin-2 (IL-2) receptor in activated T lymphocytes was examined. 1 alpha, 25(OH)2D3 enhanced the expression of IL-2 receptor (p55, Tac peptide) in phytohemagglutinin (PHA)-stimulated (3 days) human peripheral blood mononuclear cells (PBM) only in the presence of IL-2 without affecting the proliferation of the cells. This enhancement was dependent on the concentration of both IL-2 (0-1 U/ml) and 1 alpha, 25(OH)2D3(0-10(-7)M). The addition of interleukin-1 (IL-1, 0-100 U/ml), did not enhance the expression of IL-2 receptor in these cells in the presence of IL-2. Moreover, 1 alpha, 25(OH)2D3 had the same effect on two cell lines, Kit225 (an IL-2 dependent cell line established from a patient with T cell chronic lymphocytic leukemia) and YT (an IL-2 independent natural killer (NK)-like cell line from a patient with acute lymphocytic leukemia). Thus, 1 alpha, 25(OH)2D3 enhances the up-regulation of IL-2 receptor (p55) by IL-2 not only in activated T cells but also in the NK-like cell line.
Nihon Ketsueki Gakkai Zasshi 1989 Sep
PMID:1 alpha, 25-dihydroxyvitamin D3 enhances the up-regulation of interleukin-2 receptor (p55) by interleukin-2. 258 63

Ochratoxin A (OA) has been reported to affect immune function both at the level of antibody synthesis and natural killer (NK) cell activity. In the present study we demonstrate that exposure of purified human lymphocyte populations and subpopulations to the toxin will abrogate the cells' ability to respond to activating stimuli in vitro. Thus, both IL-2 production and IL-2 receptor expression of activated T lymphocytes are severely impaired. When the cells are preincubated with the analogue ochratoxin B (OB) prior to OA exposure, the inhibitory effect of OA is reversed. Furthermore, the inhibitory effect of OA on antibody production is not only due to blocking of T helper cell function. Highly purified B lymphocytes will not respond to polyclonal activators in vitro after a brief pulse with OA. The results strongly suggest that the toxin causes its immunosuppression through interference with essential processes in cell metabolism irrespective of lymphocyte population or subpopulation.
Mycopathologia 1989 Sep
PMID:Mechanism of ochratoxin A-induced immunosuppression. 261 93

Fresh lymph-borne (veiled) dendritic cells (L-DC) in the rat are almost totally negative for the interleukin-2 (IL-2) receptor detected by the monoclonal antibody (mAb) MRC OX39. After 16 hr culture more than 90% of L-DC are OX39 positive, and increased levels of expression can be seen within 5 hr culture. In cultures of L-DC and allogeneic lymphocytes. L-DC appear to express the IL-2 receptor more rapidly than lymphocytes. The intensity of labelling of L-DC is variable but maximal levels are similar to those seen on lymphoblasts. Culture in the presence of concanavalin A (Con A)-stimulated spleen cell supernatants or recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) results in a more rapid and intense expression of the IL-2 receptor by L-DC. L-DC cultured following rigorous T-cell depletion, or derived from athymic rats also express the IL-2 receptor after culture with GM-CSF. Cultured, but not fresh, L-DC bind iodinated recombinant IL-2 in a dose-dependent manner and binding is inhibited by excess unlabelled ligand. The amount of IL-2 bound varies but maximal amounts are similar to those bound by lymphoblasts. Following intravenous endotoxin injection, a large proportion of freshly collected L-DC express the IL-2 receptor and the number of L-DC released into the lymph is increased. An antibody to the IL-2 receptor which blocks an allogeneic MLR has no effect on a xenogeneic MLR using rat L-DC as stimulators and mouse lymphocytes as responders.
Immunology 1989 Sep
PMID:Properties of lymph-borne (veiled) dendritic cells in culture. II. Expression of the IL-2 receptor: role of GM-CSF. 268 Sep 7

The role of interleukin 2 (IL-2) for growth and differentiation of normal and malignant B cells still remains controversial. We assessed normal peripheral blood B cells and cell lines derived from patients with B non-Hodgkin's lymphomas (NHLs) with respect to their responsiveness to recombinant human IL-2 (rIL-2). The NHL cell lines used in our experiments expressed the Tac antigen (CD25)--a compound of the IL-2 receptor (IL-2R)--in a percentage ranging from 28 to 57%. As measured in a [3H]thymidine uptake assay, the normal peripheral blood B cells demonstrated a dose-dependent proliferative response to rIL-2, whereas the NHL cells did not show any responsiveness to rIL-2. In a clonogenic culture assay we evaluated the colony formation of the NHL cells and found a decrease of 28 to 41% on average in the presence of rIL-2 (10-50 U/ml). This moderate inhibitory effect on the clonal growth of the NHL cells was not due to a differentiation inducing effect of rIL-2, as studied by measuring the Ig production under increasing doses of rIL-2 (1 to 100 U/ml). Thus, malignant NHL B cells may express the CD25 compound of the IL-2 receptor on their surface, demonstrating a different functional responsiveness to rIL-2 compared to normal peripheral blood B cells.
Immunol Lett 1989 Sep
PMID:Effect of recombinant human interleukin 2 (rIL-2) on normal peripheral blood B cells and B lymphoblastoid cell lines. 268 Sep 16

An early consequence of stimulation of T cells via their Ag receptor is the activation of protein kinase C (PKC). It has recently been shown that PKC activity resides in a family of homologous proteins. Inasmuch as T cells are phenotypically and functionally heterogeneous, we examined the possibility that this heterogeneity may be reflected in differential expression of message for PKC isoenzyme genes. RNA from six leukemic T cell lines was probed for PKC-alpha, -beta, and -gamma message before and after activation. These studies revealed significant differences among these lines. None expressed mRNA for PKC-gamma. Whereas all cells possessed message for PKC-alpha, there was consistent variability in the level expressed. The greatest heterogeneity was seen with PKC-beta. Two cell lines, HUT 78 and HPB-ALL, did not hybridize with the beta probe under any conditions tested. We subsequently used these PKC-beta negative cells to study the role of this isoenzyme in mediating some of the effects seen with phorbol esters that directly bind to and activate PKC. Our results indicate that PKC-beta, which is expressed in some T cells, is not necessary for PMA-induced CD3 or CD4 internalization, IL-2 production, or acquisition of the p55 chain of the IL-2 receptor.
J Immunol 1989 Sep 01
PMID:Heterogeneity of protein kinase C isoenzyme gene expression in human T cell lines. Protein kinase C-beta is not required for several T cell functions. 278 92

The ability of interleukin-7 (IL-7) to stimulate murine thymocyte proliferation was investigated. IL-7, either alone or in concert with lectin, induced proliferation of adult thymocytes as well as day 13 fetal and adult CD4-/CD8-thymocytes. The IL-7-induced proliferative response of unfractionated thymocytes could not be inhibited by antibodies to IL-2, or IL-4, IL-6, or the IL-2 receptor. In addition, IL-2, IL-4, and IL-6 were not produced by thymocytes activated with IL-7, as judged by the absence of biologically active cytokine in IL-7-stimulated culture supernatants. IL-7 could act in concert with IL-2 and IL-4 or with IL-4 to enhance the proliferative response of thymocyte cultures. Thus, IL-7 may cause proliferation of thymocytes directly, not indirectly, through production of IL-2, IL-4, or IL-6. IL-7 may then play a significant role in differentiation of T lymphocytes.
Blood 1989 Sep
PMID:Murine thymocytes proliferate in direct response to interleukin-7. 278 67

The biological activity of recombinant Interleukin-2 (rIL-2) administered intraperitoneally (ip) has not been determined and may differ significantly from the maximum tolerated dose (MTD). In this trial, the pharmacokinetics, toxicity, and biologic activity of a single ip dose were studied initially followed a week later by a 5-day ip rIL-2 given for 2 weeks every 28 days. Planned dose escalation was from 2 x 10(3) to 2 x 10(7) U given in 2 liters of D5W. Drug was obtained from the NCI and was administered through an ip port. Four patients received 1 U/ml and four patients received 10 U/ml. Preliminary data demonstrate an increase in the peritoneal fluid mononuclear cell count. Mononuclear cell phenotyping tested in the first eight patients showed a modest increase in Leu 2a+, Leu 15- cells, corresponding to CTL. A similar increase in Leu 19+ cells was also demonstrated (NK cells). Soluble IL-2 receptor was elevated in peritoneal fluid. Cytotoxicity against K562 and Daudi cell lines was not observed at the first two dose levels. Toxicity of treatment was minimal and related to abdominal distention. No objective responses were seen but in one patient we documented a reduction in serum CA-125 levels. The observed biologic response and lack of toxicity is promising and justifies further exploration of this immune-modulating approach.
Gynecol Oncol 1989 Sep
PMID:Phase IB study of low-dose intraperitoneal recombinant interleukin-2 in patients with refractory advanced ovarian cancer: rationale and preliminary report. 278 2

This study was undertaken to explain the molecular basis for the diverse pathology and clinical behavior of postthymic T cell malignancies. Total cellular RNAs were extracted from four HTLV-1 positive and ten HTLV-1-negative T cell lymphomas and cell lines, and investigated for homology with cloned DNA probes specific for interleukin-2 (IL-2), IL-2 receptor (IL-2R), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and epidermal growth factor receptor (EGF-R). Tumor cells associated with clinically high grade HTLV-1-positive adult T cell leukemia (ATL) and large cell morphology (T immunoblastic lymphomas) were found to have higher levels of expression of IL-2 and TGF-beta genes than low grade T cell neoplasms (mycosis fungoides and Sezary's syndrome). High expression of IL-2R gene was restricted to Ki-1-positive lymphomas and to one ATL. Cell lines corresponding to the advanced stage of a cutaneous T cell lymphoma (CTCL) showed enhanced expression of PDGF. Therefore, high grade T cell malignancies had consistently elevated expression of growth factor/receptor (GF/R) genes. Expression of EGF-R was negligible in all T cell malignancies. An inverse relationship was found between the expression of T cell antigen receptor (differentiation antigen) and GF/R (activation antigen) genes, accounting for the frequent aberrant expression of T cell antigens in high grade T cell lymphomas. The results suggest that post-thymic T cell malignancies derived from activated T cells produce and secrete GF, conferring a growth advantage on neoplastic T cells, and correlating well with their histologic subtype and clinical behavior.
Am J Pathol 1989 Sep
PMID:Expression of growth factor/receptor genes in postthymic T cell malignancies. 278 74

Macrophage populations derived from Trypanosoma brucei-infected mice suppress both interleukin-2 (IL-2) production and IL-2 receptor expression. To try to identify the regulatory level by which the T-cell activation is switched off, we have analysed the potential of the suppressive macrophage-like cells to block the secretion of the accessory cell-derived T cell co-stimulator interleukin-1 (IL-1). The IL-1 secretion, however, was found to be greatly increased rather than decreased. The increased secretion was in part caused by an increased release rather than by an increased synthesis. In the presence of an in vitro trigger (lipopolysaccharide), the IL-1 secretion was increased 20-30-fold by the infection whereas the total IL-1 production increased only 1.5-2-fold. Macrophages from infected mice thus manifested a marginally increased IL-1 synthesis but released a markedly larger proportion of the synthesized monokine than normal macrophages. In the absence of an in vitro trigger, the infection caused a 10-15-fold increase in IL-1 synthesis as a consequence of an in vivo preactivation. This increase was only observed when the synthesis of prostaglandins was blocked by addition of indomethacin.
Immunology 1989 Sep
PMID:Modulation of IL-1 production and IL-1 release during experimental trypanosome infections. 280 68


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