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)

X-linked severe combined immunodeficiency (XSCID) is characterized by absent or profoundly reduced numbers of T cells and normal numbers of B cells in the circulation. Affected patients have mutations of the interleukin-2 (IL-2) receptor gamma chain gene. Using Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs) established from two unrelated XSCID patients, we could show that neither expressed the IL-2 receptor gamma chain on the cell surface. A novel cytokine IL-15, which has biologic activities similar to those of IL-2, could bind to the XSCID B-LCLs in the absence of the gamma chain, although both the beta and gamma chains of the human IL-2 receptor were previously shown to be required for IL-15 binding by transfected COS cells. Furthermore, a significant reduction and delay of IL-15 internalization by B lymphoblasts from XSCID patients was observed when compared with that of normal control B-LCLs. These results show the existence of a novel IL-15-specific receptor component that contributes to IL-15 binding but is insufficient for IL-15 internalization in the absence of the IL-2 receptor gamma chain.
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PMID:Characterization of B-cell lines established from two X-linked severe combined immunodeficiency patients: interleukin-15 binds to the B cells but is not internalized efficiently. 763 50

We explored the role of a new cytokine, IL-2 receptor-inducing factor (IL-2RIF), in intestinal mucosal immunity and in the regulation of integrin beta 7 receptors on intestinal lymphocytes. Most SIEL (small intestine intraepithelial lymphocytes) were M290 (alpha M290 beta 7) positive, while only 10 to 15% of SIEL were R1-2 (alpha 4) positive. The expression of alpha 4 (R1-2) and beta 7 (M293) but not alpha M290 beta 7 integrin on SIEL was up-regulated by IL-2RIF. Incubating SIEL with IL-2RIF resulted in the up-regulation of CD45RB and down-regulation of CD44. About 50% of LPL (lamina propria lymphocytes) were alpha M290 beta 7 positive, while only 20% of LPL were alpha 4 positive. The expression of alpha M290 beta 7 integrin on LPL was down-regulated and alpha 4 and beta 7 integrin was up-regulated by IL-2RIF. Incubating LPL with IL-2RIF resulted in the up-regulation of CD44 and no significant change of CD11a, CD45, CD45RB, and ICAM-1. These results suggested that SIEL and LPL may play a different role in intestinal mucosal immunity and that IL-2RIF may play an important role in regulating the functions of integrins beta 7 on IEL and LPL.
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PMID:Expression of beta 7 integrins and other cell adhesion molecules on mouse lymphocytes and their modulation by a new cytokine, IL-2 receptor-inducing factor. 763 47

This study evaluates the morphological and phenotypic changes that occur in squamous cell carcinoma of the head and neck when local infusions of interleukin-2 (IL-2) are given. Twelve patients were treated with a range of doses of IL-2 (3 x 10(3) to 3 x 10(6) international units/day) by continuous intra-arterial infusion for 10 days. Biopsies of the tumour were taken pre- and 48 h post-therapy, snap-frozen, cut, and examined histologically and immunocytochemically. Local infusions of IL-2 increase the numbers of antigen-presenting Langerhans cells (CD1a-positive) and infiltrating lymphocytes, predominantly of the CD3 and CD4 (T-helper) phenotypes. Locally infused IL-2 results in the expression of MHC (major histocompatibility complex) class II antigens on the surface of the tumour cells, capillary and post-capillary endothelial cells, and peri-tumoural macrophages. Intratumoural NK (natural killer) cells and CD8-positive (T-cytotoxic) infiltrating lymphocytes were not increased by this therapy and CD25 (IL-2 receptor) was only increased in those patients treated at the lower dose levels. The system of intra-arterial cytokine infusion into head and neck tumours developed in this study is a useful model to examine the biological effects of cytokines, since in vivo they are mainly produced and act locally. Furthermore, the infused tumours are easily accessible to biopsy. The results from studies such as this may influence the design of tumour-targeted cytokine gene therapy programmes.
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PMID:The phenotypic changes in tumour infiltrating lymphocytes and tumour cells following intra-arterial infusion of interleukin-2 in patients with squamous cell carcinoma. 763 27

Interleukin-15 (IL-15) is a novel cytokine of the four-helix bundle family which shares many biological activities with IL-2, probably due to its interaction with the IL-2 receptor beta and gamma (IL-2R beta and gamma c) chains. We report here the characterization and molecular cloning of a distinct murine IL-15R alpha chain. IL-15R alpha alone displays an affinity of binding for IL-15 equivalent to that of the heterotrimeric IL-2R for IL-2. A biologically functional heteromeric IL-15 receptor complex capable of mediating IL-15 responses was generated through reconstruction experiments in a murine myeloid cell line. IL-15R alpha is structurally similar to IL-2R alpha; together they define a new cytokine receptor family. The distribution of IL-15 and IL-15R alpha mRNA suggests that IL-15 may have biological activities distinct from IL-2.
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PMID:Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor. 764 85

Human intestinal lymphocytes, particularly intraepithelial lymphocytes, proliferate minimally to some agents, like mitogens and stimuli of the CD3 pathway. This in vitro finding may be due, in part, to a loss of factors found in vivo. Three T-cell growth factors, IL-7, IL-9, and IL-12, were tested for their ability to stimulate the proliferation of intestinal lymphocytes. Both intraepithelial lymphocytes and lamina propria lymphocytes proliferated more vigorously to IL-7 than to IL-9 or IL-12, and only IL-7 increased stimulation through the CD3 pathway. The IL-7-induced response was IL-2-dependent: IL-2 receptors appeared on both intestinal lymphocyte types, and antibody to the IL-2 receptor blocked IL-7-induced proliferation. Both CD4+ and CD8+ T-cell subsets responded to this cytokine as shown by phenotype-depletion experiments and constancy in the CD4/CD8 ratios after culture with IL-7. In addition, the T-cell receptor alpha beta and gamma delta subsets responded equally well to IL-7. This newly described selective proliferative response of intestinal lymphocytes to IL-7, but not to IL-9 or IL-12, requires no preactivation and may enhance growth in vivo.
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PMID:Interleukin-7 activates intestinal lymphocytes. 764 74

Adult T cell leukemia-derived factor (ADF)/Thioredoxin (TRX), originally defined as an IL-2 receptor alpha-chain/p55 inducer, has many cytokine-like activities. We reported that the release of major basic protein (MBP) from mature eosinophils stimulated with cytochalasin B and C5a were augmented after preincubation with recombinant ADF/TRX. The addition of a TRX specific inhibitor, BE40644, suppressed the augmentation of MBP release from mature eosinophils. It is suggested that BE40644 is applicable in allergic diseases associated with eosinophils.
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PMID:Role of ADF/TRX and its inhibitor on the release of major basic protein from human eosinophils. 765 31

The bacterial superantigen, staphylococcal enterotoxin A (SEA) activates T cells with high frequency and directs them to lyse MHC-class-II-expressing cells in superantigen-dependent cell-mediated cytotoxicity (SDCC). Treatment of mice with SEA induced strong CD8+ T-cell(CTL)-mediated SDCC, as well as abundant cytokine production from CD4+ and CD8+ T cells. However, both cytotoxicity and cytokine release were transient. In contrast, combined treatment with SEA and recombinant interleukin-2 (rIL-2) increased peak levels and maintained CTL activity. These effects were concomitant with an increased number of SEA-reactive V beta 11+ T cells. Both the CD4+ and CD8+ populations contained higher frequencies of cells expressing IL-2 receptor (IL-2R) alpha beta, which suggests that continuous IL-2R signaling preserves its high expression and subsequently prevents loss of growth factor signals necessary for expansion of T cells. Although IL-2R expression was increased among both CD4+ and CD8+ cells, only the cytotoxic function of CTL, but not cytokine production from either CD4 or CD8, was augmented. These findings demonstrate that treatment with rIL-2 potentiates superantigen-induced cytotoxicity and maintains high CTL activity. rIL-2 might therefore be useful in improving superantigen-based tumor therapy.
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PMID:Enhanced and prolonged efficacy of superantigen-induced cytotoxic T lymphocyte activity by interleukin-2 in vivo. 765 74

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TILs) causes regression of some human tumors. However, the sustained proliferation and antitumor activity of TILs requires the coadministration of potentially toxic amounts of interleukin-2 (IL-2). In an effort to overcome the requirement by T cells for IL-2, we have introduced alternative growth factor receptors that use the relatively nontoxic cytokine erythropoietin (Epo) as a ligand. In our model system, the coexpression of chimeric receptors consisting of the extracellular portion of the Epo receptor (EpoR) and the intracellular portions of the IL-2 receptor subunits, beta and gamma, conferred Epo responsiveness on a T-cell line. By contrast, cells expressing the wild-type EpoR did not proliferate in response to Epo. This suggested that Epo binding caused the activation of an IL-2 signal pathway mediated by the chimeric receptors. This approach can be used to minimize toxicity and potentially improve cancer immunotherapy with TILs.
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PMID:Acquired erythropoietin responsiveness of interleukin-2-dependent T lymphocytes retrovirally transduced with genes encoding chimeric erythropoietin/interleukin-2 receptors. 766 75

Plasma cytokine levels were examined in 13 patients with thrombotic thrombocytopenic purpura (TTP). Complete remission (CR) was attained in 7 of the 13 patients, but 6 died. Tumor necrosis factor (TNF), Interleukin (IL)-1, IL-6 and soluble IL-2 receptor showed marked increases at onset and decreased at CR. The prognosis tended to be poor in patients with increased IL-6 and soluble IL-2 receptor levels. Tissue factor production in human umbilical vein endothelial cell (HUVEC) cultured with TTP plasma was significantly increased, but the migration of HUVEC to TTP plasma was significantly lower. These findings suggest that immunological mechanisms and vascular endothelial cell damages are involved in the pathogenesis of TTP and are reflected in the plasma cytokine levels.
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PMID:[Cytokine levels in patients with thrombotic thrombocytopenic purpura]. 767 49

The intravenous injection of mice with lymphocytic choriomeningitis virus (LCMV) induces a rapid and long-lasting immunodeficiency. T lymphocytes from 7-day-infected mice do not proliferate in vitro in response to ConA stimulation, do not produce IL-2 but display high affinity IL-2 receptors on their membrane. The non-coordinated regulation of these genes suggested that other cytokine-encoding genes may also be affected in their regulation. We have thus analyzed the expression of the genes encoding different cytokines transcribed during spleen cell activation by ConA. The genes encoding T lymphocyte-derived cytokines can be classified in three groups: the genes expressed similarly by normal and LCMV-cells (the p55 and the p75 chains of the IL-2 receptor [1]), the genes under expressed in LCMV-cells (IL-2, IL-3, IL-4 and IL-5) and the genes over expressed by these cells (GM-CSF and IFN-gamma). These results show that the viral infection has provoked a profound alteration of the overall regulation of the genetic program that follows T lymphocyte activation. Since T cell activation depends strictly on accessory cell-derived cytokines, we measured the level of transcription of IL-1, IL-6 and TNF-alpha; and our data show that the expression of these genes is equivalent in normal cells and in cells from LCMV-infected mice.
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PMID:Altered cytokine genes expression by conA-activated spleen cells from mice infected by lymphocytic choriomeningitis virus. 768 35


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