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)

The mitogenic or antigenic stimulation of T lymphocytes in the presence of accessory cells results in the synthesis of interleukin-2 (IL-2), which, on interacting with de novo synthesized receptors on the membrane, induces the proliferation and differentiation of T cells. T lymphocytes are the preferential target cells of human T-lymphotropic virus type I (HTLV-I). This virus was isolated from leukaemic cells of patients with adult T-cell leukaemia. No viral transcription was detected in these leukaemic cells, indicating that consistent expression of HTLV-I is not needed for maintenance of the neoplastic state. After a short time in culture, these leukaemic cells produce viral particles which immortalize normal T cells. Hence, HTLV-I might be an important agent not only in the development, but also in the initiation, of this lymphoproliferative disease. This possibility was sustained by our previous observations indicating that normal T lymphocytes incubated with HTLV-I are able to form colonies in soft agar, seven days later, in the absence of exogenous IL-2. These results led us to explore further the immediate effects of viral infection on purified resting T lymphocytes. Here, we present evidence that HTLV-I is able to activate T lymphocytes. Indeed, binding of viral particles to these cells induces IL-2 production and IL-2 receptor expression, and triggers T-cell proliferation. This initial activation, which appears to be independent of accessory cells, may be relevant in understanding the role of HTLV-I in the aetiology of adult T-cell leukaemia.
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PMID:Direct activation of resting T lymphocytes by human T-lymphotropic virus type I. 303 13

Human recombinant interleukin 2 (hrIL-2) was demonstrated in vitro to be chemotactic for mouse large granular lymphocytes (LGL) activated in vivo by virus infection. Peritoneal exudate cells harvested from virus-infected mice were used as a source of LGL. LGL collected from mouse hepatitis virus-infected mice at 3 days postinfection were a source for NK 1.1 positive natural killer (NK)/LGL. LGL collected from mice treated with antiserum to gangliotetraosylceramide and infected with lymphocytic choriomeningitis virus for 7 days were used as a source for Lyt-2 positive cytotoxic T lymphocytes (CTL)/LGL. Both NK/LGL and CTL/LGL responded chemotactically to hrIL-2, purified IFN-beta, and to crude cell-free washout fluids collected from the peritoneal cavity of virus-infected mice. hrIL-2 had chemotactic activity for virus-elicited granular and agranular lymphocytes but did not attract the contaminating macrophages, in contrast to IFN-beta, which displayed chemotactic activity for virus-elicited granular and agranular lymphocytes as well as macrophages. The migration to hrIL-2 was inhibited by a monoclonal antibody (7D4) to the IL-2 receptor, but treatment with 7D4 did not affect migration in response to IFN-beta. Microscopic examination of Wright's-Giemsa-stained migrated NK/LGL and CTL/LGL revealed that the majority of migrated LGL in either LGL population had a blast cell morphology (enlarged cells with rich basophilic cytoplasm). The frequency of cells bearing the LGL morphology within the virus-elicited nonadherent peritoneal exudate cell population was on incubation in vitro, stabilized by either hrIL-2 or IFN-beta. These data suggest that another important immunomodulating function of IL-2 may be to attract activated NK/LGL and CTL/LGL to sites of inflammation.
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PMID:Chemotactic effect of human recombinant interleukin 2 on mouse activated large granular lymphocytes. 349 69

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

Natural killer (NK) cells are large granular lymphocytes thought to be important in the host's early immune response to viral infection and malignant transformation. NK cells proliferate and display enhanced cytotoxic activity in response to the T cell growth factor, interleukin 2 (IL-2). Stem cell factor or steel factor (SF) is the ligand for the c-kit receptor, and when combined with other hematopoietic growth factors, SF synergistically promotes the proliferation and differentiation of bone marrow stem cells. In the present study we show the c-kit receptor to be uniquely expressed on a subset of resting human NK cells (CD56bright) which constitutively expresses both the high affinity IL-2 receptor (IL-2R) and the intermediate affinity IL-2R. Other lymphocyte populations, including CD56dim NK cells, did not appear to express the c-kit receptor. Within the CD56bright NK cell subset, SF alone had no obvious effect on proliferation or cytotoxic activity. SF was shown to significantly augment the proliferative effect of IL-2, and caused a marked shift in the dose-response curve at IL-2 concentrations that selectively saturate the high affinity IL-2R. The potentiating effect of SF on NK cell proliferation was dependent on IL-2 binding to the high affinity IL-2R, and was blocked by a monoclonal antibody directed against the c-kit receptor. SF did not enhance proliferation at higher IL-2 concentrations that saturate the intermediate affinity IL-2R, nor did SF enhance IL-2-induced cytotoxic activity. Together, these data indicate that SF and IL-2 act synergistically to directly augment the proliferative capacity of a unique human NK cell subset constitutively expressing the high affinity IL-2R and the c-kit receptor. The implications of these findings on NK cell development and the host's early immune response to pathogen invasion are discussed.
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PMID:Expression of a functional c-kit receptor on a subset of natural killer cells. 768 85

The genes encoding the alpha- and beta-chains of the human interleukin-2 receptor were expressed in lepidopteran insect cells using the baculovirus expression vector system. The corresponding genes were inserted under the polyhedrin promoter of the Autographa california nuclear polyhedrosis virus and expressed in the Spodoptera frugiperda insect cell line during viral infection. The recombinant receptor proteins were identified in the insect cell lysates by using protein dot blot and ELISA techniques. At 36 h post infection the corresponding proteins were clearly detected using anti-IL-2 alpha- and beta-receptor-specific antibodies. A large amount of the alpha-chain was also found in the supernatant culture media at 72 h post infection and metabolic labelling with [35S]-methionine indicated that it was proteolytically cleaved into a 32 kDa soluble form. A similar soluble or secreted form of the beta-chain was, however, not observed. Both receptor proteins were expressed on the surface of the insect cells as determined by flow cytometry analysis. Studies performed with the different IL-2 receptor forms (alpha- and beta-chains alone or in combination) in the presence or absence of rIL-2 suggest that the receptor proteins when expressed in infected insect cells are non-functional with respect to tyrosine phosphorylation.
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PMID:Expression of human IL-2 receptor alpha- and beta-chains using the baculovirus expression system. 835 2

Cytokine response to viral infection can be of critical importance in the host defense against virus. Interferon (IFN)-gamma and interleukin (IL)-2 have wide ranges of activities in host defense mechanisms. Therefore, these cytokine genes in the liver were investigated in a series of patients with hepatitis C virus (HCV) infection using a reverse transcribed-polymerase chain reaction (RT-PCR). Total RNA was purified from liver biopsies, reverse transcribed to cDNA, amplified by specific primers, and the products were detected by agarose gel and slot blot hybridization. All samples from acute hepatitis (AH; n = 4) and chronic hepatitis patients (CH; n = 19) were positive for IFN-gamma at varying degrees. AH patients showed strong signals compared to CH patients, liver cirrhosis (LC; n = 12; 72% positive) patients, and hepatocellular carcinoma (HCC; n = 21; 19% positive) patients. IL-2 gene was undetectable in all patients tested. IL-2 receptor (IL-2R) was detectable in AH, CH and LC patients but not in HCC patients. We conclude that IFN-gamma has important roles in the cytokine network that indeed present in the liver of HCV patients while the presence of IL-2R gene may indicate that the signaling pathway for IL-2 is intact.
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PMID:Interferon-gamma, interleukin (IL)-2 and IL-2 receptor expressions in hepatitis C virus-infected liver. 839 42

The marked tropism of human herpesvirus-6 (HHV-6) for natural killer (NK) cells and T lymphocytes has led us to investigate the effect of HHV-6 on cellular cytotoxicity. We describe here how HHV-6 infection of peripheral blood mononuclear cells (PBMC) leads to upregulation of their NK cell cytotoxicity. The induction of NK cell activity by HHV-6 was abrogated by monoclonal antibodies (mAbs) to IL-15 but not by mAbs to other cytokines (IFN-alpha, IFN-gamma, TNF-alpha, TNF-beta, IL-2, IL-12) suggesting that IL-15 secreted in response to viral infection was responsible for the observed effect. Furthermore, NK activation by HHV-6 was blocked with mAb to CD122, as well as by human anti-HHV-6 neutralizing antibodies. Using RT-PCR, we were able to detect IL-15 mRNA upregulation in purified monocyte and NK cell preparations. IL-15 protein synthesis was increased in response to HHV-6. Finally, addition of IL-15 to PBMC cultures was found to severely curtail HHV-6 expression. Taken together, our data suggest that enhanced NK activity in response to viral infection represent a natural anti-viral defense mechanism aimed at rapidly eliminating virus-infected cells.
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PMID:Human herpesvirus-6 enhances natural killer cell cytotoxicity via IL-15. 861 68

The paper is a review of the literature on cellular and humoral immunity in schizophrenic patients. The reports have revealed that there are manifestations of autoimmunological process in a subgroup of schizophrenics (among others: increased serum level of specific and non-specific autoantibodies, decreased lymphocyte interleukin-2 production, increased soluble IL-2 receptor concentration, increased serum IL-6 level, presence of lymphocyte abnormalities and association with HLA antigens. It is suggested that virus infection may provoke the appearance of autoimmunological reaction, while genetic factors might increase some predisposition to this reaction. The reports have also revealed that autoimmunity may play a role in pathogenesis of schizophrenia in a subgroup of schizophrenic patients who have immunological abnormalities.
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PMID:[Changes of humoral and cellular immunity in schizophrenia]. 898 18

In a previous study (Tsukui et al., Cancer Res., 56: 3967-3974, 1996), we observed an inverse association between degree of cervical neoplasia and interleukin (IL) 2 production by peripheral blood mononuclear cells in response to human papillomavirus (HPV) 16 E6 and E7 peptides in vitro. This suggested that a Th1-mediated cellular immune response might be important in host immunological control of HPV infection and that a lack of such a response might predispose to progression of cervical disease. To follow up on these findings, we have conducted a cross-sectional study of women with various degrees of cervical neoplasia to investigate the association between overall immune activation and cervical disease. A total of 235 women were recruited into our study; 120 of these women were participants in our previous study in which IL-2 production in response to HPV-16-specific peptides was measured. The study population included 34 women with invasive cancer, 62 women with high-grade squamous intraepithelial lesions (HSILs), and 105 women with low-grade squamous intraepithelial lesions (LSILs). In addition, 34 cytologically normal women with no past history of squamous intraepithelial lesions despite confirmed HPV-16 infection in the 5 years preceding the study were selected as controls. As our measure of overall immune activation, serum samples obtained from study participants were tested for soluble IL-2 receptor (sIL-2R) level using an ELISA method. The mean sIL-2R levels were found to increase with increasing disease severity (Ptrend = 0.0002). Among cytologically normal, HPV-exposed women, the mean receptor level in serum was 465.8 units/ml compared to 467.6 units/ml among LSIL subjects, 514.9 units/ml among HSIL subjects, and 695.5 units/ml among women with invasive cervical cancer. Similarly, the proportion of women with elevated sIL-2R levels (defined as > or = 450 units/ml) increased with increasing disease severity from 35.2% among normal study subjects to 70.6% among cancer patients (Ptrend = 0.003). Among the subgroup of subjects for whom in vitro IL-2 production in response to HPV-16-specific peptides was measured, we examined the association between in vitro IL-2 production and serum levels of sIL-2R. sIL-2R levels were higher, on average, among those women who were positive in our IL-2 production assay compared to those who were negative, but the differences did not reach statistical significance (P > 0.05). We also observed a trend of increasing sIL-2R level with increasing disease severity both in women who were positive and in women who were negative for our IL-2 production assay, but the trend was only significant among those who were negative for IL-2 production (Ptrend = 0.01). Results from our studies suggest that although the immune system of women with cervical neoplasia is nonspecifically activated as disease severity increases, the ability of those women with HSILs or cancer to mount a Th1-mediated immune response to HPV peptides appears to decrease compared to women with LSILs or normal women infected with HPV. Increased overall activation along with decreased Th1 immune response among women with increasing cervical disease severity might be explained by an increased Th2-mediated immune response, a response that we hypothesize is ineffective in controlling the viral infection and its early cytological manifestations. Future studies should directly assess Th2-mediated responses to confirm this hypothesis. Also, future efforts should be aimed at determining whether the associations observed are causally related to disease progression or an effect of the disease.
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PMID:Immune activation in cervical neoplasia: cross-sectional association between plasma soluble interleukin 2 receptor levels and disease. 933 63

NK cells, a key component of the innate immune system, are known to play an important role against viral infections. Previously, we reported that the human herpesvirus-6 (HHV-6) induces IL-15 in human PBMC and increases their NK activity. We describe in this work that another human herpesvirus, HHV-7, which shares genomic homology with HHV-6, also causes up-regulation of NK cell cytotoxicity via IL-15 induction. The NK cell activity of the PBMC from different donors displayed a variable range of enhancement after treatment with HHV-7. This enhancement occurred within a few hours of exposure to the virus and was blocked by Abs to IL-15, but not to other cytotoxicity-enhancing cytokines (i.e., to IFN-gamma, IL-2, TNF-alpha, or IL-12). Our results also show that this HHV-7-induced IL-15-mediated activation of NK cells occurs via IL-2R, since HHV-7-enhanced NK cytotoxic activity could be blocked completely by anti-IL-2R beta-chain mAb (anti-CD122). The up-regulation of NK cell cytotoxicity did not require infectious virus, as the use of UV-irradiated HHV-7 produced similar results. This effect was virus specific because it was abrogated by neutralizing the virus with human sera containing Abs to HHV-7. We also found increased amount of IL-15 transcripts in HHV-7-treated PBMC as compared with the untreated PBMC. Taken together, these results would suggest that host responds to HHV-7 infection by up-regulating IL-15 production, which then results in an enhancement of NK cell activity; this, in turn, may play a major role in the control of the viral infection.
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PMID:Enhancement of natural killer cell cytotoxicity by the human herpesvirus-7 via IL-15 induction. 936 23


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