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 response of the human CD4+ T-cell line Jurkat to infection with vaccinia virus was investigated. Virus titers peaked approximately 3 to 4 days after infection, while cell growth paralleled that of uninfected cells, indicating that growth rates were not appreciably affected by viral infection. Results from plaque assays and fluorescence-activated cell sorter (FACS) analyses of virus antigens demonstrated that a persistent infection in which the percentage of infected cells and the virus titers fluctuated from passage to passage was established. Further characterization of the persistent infection revealed that the virus influences cellular functions. Induction of interleukin-2 (IL-2) and IL-2 receptor alpha (IL-2R alpha) in Jvac cells was shown by enzyme-linked immunosorbent assay and FACS analysis, respectively. Hybridization of cellular RNA with cloned probes confirmed the increased IL-2 expression and demonstrated that Jvac cells also expressed more IL-6 but not gamma interferon (IFN-gamma) or IL-1 beta. Dual-antibody staining and FACS analysis for vaccinia virus antigens and IL-2R alpha indicated that IL-2R alpha expression was restricted to the infected cells. Jvac cells were also resistant to superinfection, an additional proof that persistent infection elicited phenotypic changes in the cell population.
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PMID:Stimulation of lymphokines in Jurkat cells persistently infected with vaccinia virus. 134 94

Hemophagocytic lymphohistiocytosis, terminology that designates a syndrome that may be familial or sporadic, with or without an associated viral infection, is presented as the prototype of a hemophagocytic syndrome, a condition in which there is uncontrolled activation of the cellular immune system. Diagnostic criteria include idiopathic fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and the presence of hemophagocytosis. The surgical and autopsy pathology features infiltrates composed of lymphocytes and ordinary, but activated, histiocytes and hemophagocytosis. The chronic hepatitis-like hepatic lesion is noted to be characteristic, if not unique, in this age group and setting. Current concepts of pathophysiology focus on the role of cytokines, particularly interleukin (IL)-1, IL-2, soluble IL-2 receptor, plasminogen activator, and prostaglandins. The clinicopathologic features of the syndrome can be accounted for by the uncontrolled and unopposed production and release of these mediators. Nosology places hemophagocytic lymphohistiocytosis in the position of the most important of the "benign" histiocytosis syndromes that involve ordinary histiocytes of the mononuclear phagocytic system in contrast to Langerhans cell histiocytosis (histiocytosis X) in which pathological dendritic histiocytes are operative. Features that distinguish hemophagocytic lymphohistiocytosis from other disorders, such as malignant histiocytosis, X-linked lymphoproliferative disorder, congenital immunodeficiency states, the accelerated phase of Chediak-Higashi syndrome, and cytophagic histiocytic panniculitis, which may be associated with a hemophagocytic syndrome, are presented.
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PMID:Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. 156 89

In this study, we have used radiolabeled IL-2 binding assays, Northern blot analysis, immunofluorescent flow cytometry and cell sorting, as well as proliferation and cytotoxicity assays to perform an extensive phenotypic and functional characterization of the IL-2 receptor in normal resting human peripheral blood lymphocytes. Our results indicate that almost all T cells (greater than 98%) express neither the high affinity IL-2 receptor nor the functional intermediate affinity p75 chain of the IL-2 receptor without prior activation. In contrast, most NK cells constitutively express the isolated intermediate affinity p75 IL-2 receptor. In addition, a subpopulation of NK cells, distinguished by high density expression of the NKH1 antigen, constitutively express the high affinity IL-2 receptor, in addition to an excess of the isolated intermediate affinity p75 IL-2 receptor. These NKH1bright+ cells exhibit a brisk proliferative response to IL-2, similar to that seen with antigen-activated T cells, yet do so in the absence of any known antigenic stimuli. No other resting peripheral blood lymphocyte population, including CD4+, CD8+, and CD20 cells, exhibits this property. The intermediate affinity p75 IL-2 receptor, as it exists in its isolated form on resting NK cells, does not transduce a growth signal equivalent to that seen in NK cells expressing the high affinity IL-2 receptor, despite doses of IL-2 that are known to fully saturate the isolated p75 chain. This strongly suggests that additional structural or functional components are involved in generating the proliferative response following the binding of IL-2 to the high affinity heterodimeric form of the IL-2 receptor. The constitutive expression of this functional high affinity IL-2 receptor on a small population of resting NK cells provides further evidence in support of a role for these cells in the host's early defense against viral infection or malignant transformation, before the more delayed but specific T cell response.
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PMID:Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors. 169 80

In natural measles virus infection, evidence of intense immune system activation is present simultaneously with clinically relevant immune suppression. While evidence of activation is most prominent early in the disease, skin test responses and in vitro lymphoproliferation are depressed for weeks after the onset of the rash. It is not known whether the prolonged period of reduced immune responsiveness results from a single defect or a succession of different abnormalities. To gain further insight into measles-induced immune suppression we studied the production of soluble IL-2 receptor (sIL-2R), interferon-gamma (IFN-gamma), IL-1 beta, and tumor necrosis factor (TNF alpha) by peripheral blood mononuclear cells (PBMC) isolated from measles patients at various times after the onset of the rash. Studies included addition of supplemental recombinant IL-1 beta (rIL-1 beta) or recombinant IL-2 (rIL-2) or suppression of prostaglandin synthesis by indomethacin (IM). Proliferation in response to phytohemagglutin (PHA) was abnormal at all stages of disease. During the acute phase (first week after the onset of the rash) spontaneous production of sIL-2R was increased (76 +/- 54 vs. controls 4 +/- 4; P less than 0.03), suggesting in vivo T cell activation while PHA-induced sIL-2R was decreased (228 +/- 43 vs. control 582 +/- 127; P less than 0.002), suggesting that the capacity to produce IL-2 in response to mitogen was limited. Supplementation of PHA-stimulated cultures with rIL-2 improved but did not normalize both proliferation (58,600 +/- 4900 to 70,700 +/- 4400 vs. control 97,700 +/- 15,500; P less than 0.03) and sIL-2R levels (114 +/- 58 to 309 +/- 87 vs. control 582 +/- 127; P less than 0.003). Both spontaneous (25 +/- 18 vs. control 237 +/- 92; P less than 0.002) and PHA-induced (20 +/- 20 vs. control 604 +/- 129; P less than 0.004) TNF alpha levels were subnormal and were not improved with rIL-2, rIL-1 beta, or IM, suggesting a block in monocyte TNF alpha production. Spontaneous and PHA-induced IFN-gamma and IL-1 beta levels were normal. During the convalescent phase (greater than 2 weeks after the onset of the rash), spontaneous levels of sIL-2R were normal and PHA-induced levels were completely normalized with supplemental rIL-2 but proliferation remained below normal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytokine production in vitro and the lymphoproliferative defect of natural measles virus infection. 191 59

It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF.
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PMID:Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue. 193 40

The immunosuppressive agent, cyclosporin A (CsA) blocks production of IL-2 by lymphocytes in vitro, and impairs immune responses in vivo. During infection of mice with lymphocytic choriomeningitis virus (LCMV), IL-2 is produced by spleen lymphocytes with a time course corresponding to that of T cell activation and proliferation, but distinct from NK cell activation and proliferation. To evaluate the requirement for IL-2 in supporting lymphocyte proliferation in vivo, and to investigate the mechanisms of CsA-induced immunosuppression, the effects of CsA on LCMV-elicited responses were examined. CsA had profound effects on lymphocyte expansion and CTL activation on day 7 postinfection, the peak of the T cell response to LCMV. Proliferation of both the CD4+ and CD8+ T cell subsets was affected. Inhibition of T cell expansion was accompanied by the inhibition of IL-2 production and IL-2 responsiveness. In situ hybridization revealed a 50% reduction in the percentage of cells transcribing IL-2, suggesting that CsA blocked IL-2 production at the level of gene transcription. Transcripts of the gene for the IL-2R p55 chain are also normally elevated during infection, and CsA treatment resulted in an 80% reduction in the percentage of cells transcribing this gene. A reduced responsiveness of freshly isolated cells to rIL-2 in vitro correlated with the reduction of IL-2 receptor gene transcription positive cells. In contrast to effects of the drug on T cells, the level of NK cell activation was not decreased as a result of CsA treatment. These observations suggest that the IL-2 produced by lymphocytes in vivo in response to virus infection is required to promote the T cell response to LCMV, but do not support a role for IL-2 in NK cell activation under the conditions examined. Furthermore, the data demonstrate the profound inhibition of lymphocyte proliferation induced by CsA treatment during an in vivo immune response.
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PMID:Effects of cyclosporin A on IL-2 production and lymphocyte proliferation during infection of mice with lymphocytic choriomeningitis virus. 196 65

The development of T-cell lymphomas in rodents infected with type C retroviruses has been linked to the generation of a class of envelope (env) recombinant viruses called mink cell focus-forming viruses (MCF viruses) in the preleukemic thymus. To determine whether infection by MCF viruses altered the growth phenotype of retrovirus-induced T-cell lymphomas, a Moloney murine leukemia virus-induced interleukin-2 (IL-2)-dependent rat T-cell lymphoma line (4437A) was infected with MCF-247, modified MCF-V33 (mMCF-V33), or NZB-xenotropic (NZB-X) virus. The effects of virus infection on the IL-2 dependence of these cells was examined by cultivating them in the absence of IL-2. After IL-2 withdrawal, the uninfected and NZB-X-infected cells went through a crisis period characterized by massive death. All the independently maintained cultures of MCF- and mMCF-V33-infected cells, on the other hand, became IL-2 independent without a crisis. All the polytropic virus-infected IL-2-independent cultures contained a population of cells that was polyclonal with regard to polytropic provirus integration. Over this polyclonal background each culture produced multiple clones of cells that were selected rapidly after IL-2 withdrawal. Furthermore, the resulting MCF- or mMCF-V33-infected IL-2-independent cells retained the expression of IL-2 receptor. These data show that MCF and mMCF-V33 viruses may alter the growth phenotype of a T-cell lymphoma line and suggest that their effect on cell growth may be due to the direct interaction of the MCF envelope glycoprotein with cellular components, perhaps the IL-2 receptor.
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PMID:Infection by mink cell focus-forming viruses confers interleukin 2 (IL-2) independence to an IL-2-dependent rat T-cell lymphoma line. 205 45

Evidence is presented that LDH virus infection of mice results in drastic changes in several immune activities. Serum IFN titer and splenic NK activity are increased during the acute phase of infection. NK stimulation is mediated by IFN-alpha,beta since injection of an antibody against murine IFN-alpha,beta is able to abolish the effect. IL-2 production is inhibited throughout the study period following injection of LDH virus (14 days), although a partial recovery is observed during the second week. Similarly, IL-2 receptor expression and MLC responsiveness are suppressed. This suppression lasts for 2 and 7 days respectively after injection. Addition of recombinant IL-2, but not of indomethacin, to the MLC cultures restores the proliferation rate. Not only proliferation but also cytotoxic cell generation in MLC is diminished during the first week after LDH virus injection. Again, this response is normalized at day 14. Additional observations indicate that LDH virus is present in murine neuroblastoma. This explains some of the previously described effects of this tumor on the cellular immune system of the host.
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PMID:Cellular immunity changes caused by LDH virus: analogy with observations of neuroblastoma-bearing mice. 244 3

HIV infection is known to induce a progressive T helper/inducer (CD4) lymphopenia and to impair the functional activities of residual cells. The present studies examined the relationship between the CD4 cell count and three functional assays: T cell colony formation in semisolid media, the capacity of PHA-stimulated cells to express IL-2 receptors, and their ability to synthesize and secrete IL-2. Cells from antibody-positive homosexuals with normal numbers of CD4 cells (greater than 700/microliters) showed defective reactivity in two assays, colony growth, and IL-2 receptor expression. These defects became progressively more pronounced in homosexuals with moderate (400-700 cells/microliters) and severe (less than 400/microliters) reductions in assays for IL-2 production by PHA-stimulated lymphocytes. Mixing experiments suggest that cells from HIV-infected men nonspecifically inhibit the colony growth of normal cells; this abnormality could be reversed by addition of exogenous IL-2. These data suggest that defective colony growth and reduced IL-2 expression are functional abnormalities directly resulting from HIV infection. Furthermore, these changes can precede the CD4 lymphopenia induced by this viral infection.
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PMID:Defective T cell colony formation and IL-2 receptor expression in HIV-infected homosexuals: relationship between functional abnormalities and CD4 cell numbers. 252 69

A 57-year-old man with a history of recurrent infections from the age of 50 was hospitalized with a diagnosis of common variable hypogammaglobulinemia (CVH). Immunological studies revealed a severe reduction of circulating immunoglobulins of all classes. Immunophenotyping of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies, revealed normal values of total B and T cells with CD4/CD8 ratio sharply reduced (0.35) as compared to normal (1.6) because of an increase of CD8 and a decrease of CD4 cells. The surface expression of IL-2 receptor was normal. Natural cytotoxic and phagocytic system presented several abnormalities: a deep impairment of NK activity was found in spite of a normal number of NK cells, as ascertained by Leu 19 and B73.1 monoclonal antibodies. The defective NK activity was not restored by interferon alfa, but was normalized by recombinant IL-2. Phagocytic function, as defined by zymosan-stimulated O2- production was almost absent. The involvement of natural cytotoxic and phagocytic systems in CVH has been rarely reported; the possible causative role of a chronic viral infection (Epstein-Barr virus?) is discussed, on the base of anamnesis.
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PMID:NK cell activity and monocyte dysfunctions in a patient with common variable hypogammaglobulinemia. 297 23


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