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)

Expression of the IL-2 receptor (Tac antigen/CD25) is documented in malignant lymphomas. Because IL-2 is a major lymphocyte growth factor, an IL-2-dependent growth could be involved in the proliferation of Tac-positive lymphomas. Indeed such a mechanism has been demonstrated experimentally for the growth of T-cell lines. To investigate this point in human lymphomas, we used in situ hybridization to analyze the expression of the IL-2 gene in 20 non-Hodgkin's lymphomas, among which 12 expressed the IL-2 receptor. Nine of these were anaplastic large cell lymphomas expressing the Ki-1-related antigen. We here show that IL-2-producing cells are present in all the lymphomas we analyzed. As a mean, there is no significant difference in the percentage of IL-2-producing cells between Tac-positive and -negative lymphomas. However, the level of IL-2 production is highly heterogeneous in both groups, and the highest density of IL-2-producing cells was observed in 2 Tac-positive lymphomas. Simultaneous detection of cellular antigens and of IL-2 mRNA demonstrates that IL-2 is produced by reactive T cells rather than by tumor cells. These results suggest that if IL-2 is involved in the growth of Tac-positive lymphomas, it acts as a paracrine, rather than an autocrine, factor.
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PMID:IL-2 mRNA expression in Tac-positive malignant lymphomas. 230 33

A human B cell line which shows a marked dose dependence on B cell growth factor (BCGF) when cultured in less than or equal to 2% serum has been established. Human B lymphocytes were obtained from peripheral blood of normal donors and cultured in the presence of anti-IgM (mu chain specific) and BCGF. Frequent refeedings with fresh medium containing BCGF and anti-IgM led to the establishment of a long term cultured human B cell line, HAB-40. Phenotyping of HAB-40 revealed that the cell population consisted predominantly of IgM-bearing (72%) and B1 (100%) positive cells. This B cell line consistently secreted IgM and IgG when co-cultured in the presence of PMA, anti-IgM and beta or gamma interferon (IFN). Also, it was Epstein-Barr virus nuclear antigen (EBNA) positive (100%). HAB-40 cells have been successfully maintained in the presence of BCGF without anti-IgM for over a year. Removal of BCGF led to the rapid loss of viable cells in cultures containing less than 2% serum. HAB-40 cells in microassays exhibited a marked dose-dependent incorporation of [3H]thymidine in response to BCGF in the absence of any exogenous stimulants such as anti-IgM or Staphylococcus aureus Cowan I (SAC). Recombinant interleukin 2 (IL-2) failed to augment the [3H]thymidine uptake by these B cells despite the low density expression of Tac antigen (IL-2 receptor) on their cell surface, or even when the cells were stimulated with phorbol myristate acetate (PMA) to express higher density of Tac antigen (48%). HAB-40 cells could be maintained in BCGF which was partially purified to deplete it of other contaminating proteins. None of the seven well established EBNA-positive human B cell lines nor two chronic B lymphocytic leukemia (B-CLL) cell lines that were tested showed BCGF dependence. The same BCGF-active chromatographic fractions that were active on HAB-40 cells also stimulated BCL1 and normal human B cells stimulated with anti-IgM. In the presence of less than or equal to 2% serum proteins this cell line provides a simple, reproducible assay for BCGF even in the presence of contaminant IL-2.
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PMID:Establishment of a human B cell line that proliferates in response to B cell growth factor. 242 13

Human T lymphocytes cultured in vitro for 5 days with C. albicans purified polysaccharide (MPPS) and with purified protein derivative (PPD) from M. tuberculosis produce an antigen nonspecific inhibitory factor(s) (nsINH). nsINH blocks antigen-driven cell proliferation and the development of natural killer cells (NK) when added at the beginning of peripheral blood mononuclear cell culture. Analysis of the mechanism of action shows that nsINH inhibits the production of interleukin 2 (IL-2), the expression of IL-2 receptor (Tac antigen), and the synthesis of immune interferon (IFN). The biochemical characterization of nsINH shows that the suppressive activity is acid (pH 2.5) and temperature (56 degrees C) resistant. Gel filtration analysis indicates a molecular weight of 30-35K and 60-65K. These results suggest a role for nsINH in the down regulation of the lymphokine cascade.
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PMID:Mechanism of action of an antigen nonspecific inhibitory factor produced by human T cells stimulated by MPPS and PPD. 242 24

A panel of human T cell clones bearing exclusively the T4 (helper) phenotype and demonstrating specificity to a well-characterized soluble glycoprotein antigen (185,000 dalton streptococcal antigen, SA) is described. After having been cultured in exogenous interleukin 2 (IL-2) for 7 days in the absence of the specific antigen, two of the clones, namely SA1.4 and SA1.23, show stronger proliferative responses to the ligand as compared to the other T4 clones. Analysis of both the high- and low-affinity IL-2 receptor (IL-2R) levels reveals that IL-2 mediates differential regulation of high affinity IL-2R expression on these antigen-deprived cloned cells. Higher levels of surface expression of the IL-2 binding sites on SA1.4 and SA1.23 as compared to the other clones are observed throughout the 7-day culture period that these lymphocytes are maintained in exogenous IL-2. All the cloned cells appear to have returned to their "unstimulated states" as noted by their stable low expressions of Tac antigen and high affinity IL-2R. The unstimulated states of SA1.4 and SA1.23 are represented by higher levels of high affinity IL-2R expression. Under the condition in which the cloned cells are exposed to a decreasing concentration of IL-2, SA1.4 and SA1.23 are found to secrete a greater amount of IFN-gamma. The present results therefore suggest that a control mechanism involving the "mutual amplification" of IL-2 and IFN-gamma regulates the differential expression of high affinity IL-2R on antigen-specific T4 clones.
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PMID:Differential regulation of interleukin 2 (IL-2) receptor expression on antigen-specific human T cell clones by IL-2. 245 Aug 41

The monoclonal antibody (mAb) AHT-107 recognized a determinant distal to the interleukin 2 (IL-2) binding site on the p55 subunit of the IL-2 receptor (IL-2R) (the Tac antigen, CD25) of human T lymphoblasts, while the mAb AHT-54 recognized a determinant close to the IL-2 binding site as did the anti-Tac. The AHT-107 inhibited IL-2 dependent proliferation of human T lymphoblasts equally as well as did the AHT-54. Both mAbs inhibited the high-affinity binding and crosslinking of IL-2 to the p55 + p75 heterodimeric complex on forskolin-treated YT cells. Remarkably, the AHT-107 did not inhibit the low-affinity binding and cross-linking of IL-2 to the p55 molecule on human p55 cDNA-transfected cells, while the AHT-54 as well as anti-Tac did so. In contrast, the mAb PC61, that was previously reported to recognize a determinant distal to the IL-2 binding site on the mouse p55 subunit of IL-2R and to dissociate IL-2 from the high-affinity IL-2R complex by altering the conformation of the p55 molecule itself, inhibited the low-affinity binding and cross-linking of IL-2 to the p55 molecule on mouse p55 cDNA-transfected cells. Further, we showed that the AHT-107 did not dissociate IL-2 from the high-affinity IL-2R complex once formed on human T lymphoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on the formation of high-affinity IL-2 binding sites of an IL-2 receptor p55 + p75 heterodimeric complex: functional importance of a determinant on the p55 subunit defined by a monoclonal antibody AHT-107. 246 50

Interleukin-2 (IL-2) responsiveness of Dermatophagoides farinae (Df)-stimulated lymphocytes from children with bronchial asthma was studied. Six-day culture of lymphocytes from allergic patients increased after an additional 3 days of incubation with recombinant IL-2. This phenomenon was not observed when the lymphocytes of patients allergic to Df were stimulated with ovalbumin (OVA). Normal lymphocytes stimulated with Df expressed Tac antigen (low-affinity IL-2 receptor) but, in contrast to the patients' lymphocytes, did not absorb nor respond to IL-2. Nonadherent responder cells cultured with Df-pulsed autologous adherent cells acquired IL-2 responsiveness, but those cultured with OVA-pulsed adherent cells did not. The monoclonal antibody to HLA-DQ framework (Leu 10 and clonab DQ), but not to HLA-DR framework (OKIa1) and HLA-DP (HLA-DP and clonab DP-DR), blocked the antigen-presenting cells from inducing IL-2 responsiveness. Nonadherent responder cells depleted of OKT4 (CD4)-positive cells failed to acquire IL-2 responsiveness, whereas depletion of OKT8 (CD8) cells had no impact. Taken as a whole, the results indicate that DQ-bearing adherent cells from allergic donors play a key role in presenting Df antigen to allergen-specific responder T cells, which are very likely to be members of the OKT4 positive subset.
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PMID:Allergen-specific induction of interleukin-2 (IL-2) responsiveness in lymphocytes from children with asthma. I. Antigen specificity and initial events of the induction. 247 92

The low affinity IgE receptors (Fc epsilon RII/CD23) homologous to animal lectins have the unique property of cleaving-off the extracytoplasmic portion as the soluble form (IgE binding factor; IgE-BF). Molecular analysis using Fc epsilon RII/CD23 cDNA proved that Fc epsilon RII is not unique to B lymphocytes but is expressed on a variety of cell lineages including T lymphocytes, macrophages and eosinophils. In these cell types, IL-4 is a general inducer of this molecule while IFN-gamma down-regulates B cell Fc epsilon RII/CD23 and up-regulates Fc epsilon RII/CD23 on macrophage and eosinophil cell lines. As predicted by the expression of Fc epsilon RII/CD23 in some HTLV-1(+) T cell lines, Fc epsilon RII/CD23 proved to be induced on normal peripheral T lymphocytes by IL-4 or IL-2 in the presence of additional permissive signals. As indicated by IL-2-dependent Fc epsilon RII/CD23 induction, there is an interesting bilateral co-regulation between Fc epsilon RII/CD23 and the 55 kDa chain of the IL-2 receptor complex with Tac antigen (IL-2R/p55(Tac]. Triggering of Fc epsilon RII/CD23 resulted in the enhanced expression of IL-2R/p55(Tac), whereas IL-2 enhanced the expression of Fc epsilon RII/CD23 in some systems. It is suggested that the triggering of cell surface Fc epsilon RII/CD23 by natural ligands is effectively buffered by soluble Fc epsilon RII/CD23 (IgE-BF).
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PMID:Low affinity IgE receptors: regulation and functional roles in cell activation. 253 50

CD28 is an antigen of 44 kDa which is expressed on the membrane of the majority of human T cells. The present study examines the functional effects of an anti-CD28 monoclonal antibody (mAb 9.3) on T cell activation induced with immobilized anti-CD3 mAb OKT3 or with mitogens, in the absence of accessory cells. To this end, we used blood resting T cells that were completely depleted of accessory cells (monocytes, B cells, and natural killer cells), and consequently did not respond to recombinant interleukin-2 (rIL-2), to immobilized OKT3, to PHA, or to Con A. Addition of mAb 9.3 to the cultures enhanced IL-2 receptor expression (Tac antigen) on PHA- or immobilized OKT3-stimulated T cells and induced IL-2 receptors on Con A-stimulated T cells. Moreover, addition of mAb 9.3 to cultures of T cells stimulated with PHA, Con A, or immobilized OKT3 resulted in IL-2 production. Soluble mAb 9.3 was a sufficient helper signal for T cell proliferation in response to PHA or immobilized OKT3. Crosslinking of mAb 9.3 by culture on anti-mouse IgG-coated plates enhanced the helper effect and was an essential requirement for the induction of T cell proliferation in response to Con A. No other anti-T cell mAb (anti-CD2, -CD4, -CD5, -CD7, -CD8) was found to provide a complete accessory signal for PHA or Con A stimulation of purified T cells. T cell proliferation induced by the combination of PHA and mAb 9.3 was strongly inhibited by the anti-IL-2 receptor mAb anti-Tac. In conclusion, mAb 9.3 can provide a signal bypassing monocyte requirement in T cell activation with immobilized OKT3, PHA, and Con A, resulting in an autocrine IL-2-dependent pathway of proliferation.
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PMID:The anti-T cell monoclonal antibody 9.3 (anti-CD28) provides a helper signal and bypasses the need for accessory cells in T cell activation with immobilized anti-CD3 and mitogens. 253 66

The characteristics of a novel T lineage-specific activation antigen, termed TLiSA1, are described. The antigen was detected with a mouse monoclonal antibody, LeoA1, that was raised against activated human T cells generated in mixed lymphocyte culture (MLC). The antigen became strongly expressed on T cells 48-72 h after stimulation with phytohemagglutinin, and retained expression on MLC-activated T cells after 10 d of culture. The antigen was absent from a range of human T, B, myeloid, fibroblast, and tumour cell lines, but was present on the surface of the interleukin 2 (IL-2)-dependent gibbon cell line MLA-144. Analysis of the antigen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitates obtained from activated human T cells demonstrated a broad band in the region of 70 kD, whereas precipitates obtained from MLA-144 revealed a single narrow band of 95 kD. The molecule was expressed with a maximum density of 66,000 copies per cell on the surface of MLC-activated T cell blasts, as assessed by Scatchard analysis. TLiSA1 was distinguished from the IL-2 receptor bound by the anti-Tac monoclonal antibody by demonstrating that the antigens did not comodulate or coprecipitate, and by constructing an IL-2-independent human T X T hybrid that expressed the TLiSA1 but not the Tac antigen. MLC with B lymphoblasts was used to generate cytotoxic T lymphocytes (CTL) specific for the stimulating cell, and anomalous killer (AK) cells able to kill melanoma target cells. The presence of LeoA1 or F(ab')2 fragments of the antibody from the beginning of coculture did not affect proliferation in these cultures, but did inhibit the induction of both CTL and AK cells from their precursors. This inhibition of differentiation by LeoA1 was confirmed under conditions of limiting dilution, where it was shown that the antibody reduced the frequency of CTL produced, and greatly (fourfold) reduced the frequency of AK cells generated from their precursors. We discuss the possibility that human CTL may express a differentiation factor receptor that is distinct from the receptor for IL-2.
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PMID:TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. 258 Sep 33

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration.
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PMID:Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro. 258 97


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