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)

Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV-) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV- and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P<0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-alpha]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV- PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-alpha mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P<0.05) and TNF-alpha (P<0.005), compared to HIV- PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-alpha) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.
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PMID:Cytokine gene expression occurs more rapidly in stimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected persons. 1097 52

We report a case of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) which developed after chemotherapy for hemophagocytic lymphohistiocytosis (HLH), who had no history of immunodeficiency or familial X-linked LPD. In HLH, the presence of EBV in T-cells was confirmed by a combination of in situ hybridization (ISH) and immunostaining. Southern blot analysis using EBV-TR and immunoglobulin JH probes revealed oligoclonal proliferation of B-cells in each organ involved by abnormal B-lymphoid cells at autopsy. Combined ISH and immunostaining disclosed the presence of EBV in proliferating B-cells. Cytokine analysis during the period of T-cell activation in HLH revealed marked elevation of interferon (IFN) gamma, interleukin (IL)-10 and soluble IL-2 receptor (sIL-2R) and mild to moderate increases of tumor necrosis factor (TNF)-alpha were observed, while IFN gamma, IL-10 and sIL-2R were elevated initially during the HLH phase, which then decreased as LPD developed and B-cell proliferation predominated. Immunosuppressive chemotherapy for HLH may then have allowed latent EBV in B lymphocytes to induce transformation and oligoclonal proliferation of B-cells, finally resulting in LPD. Mechanisms of EBV-induced cell proliferation remain unclear, but alteration of various cytokines may be responsible for it.
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PMID:Epstein-Barr virus (EBV)-induced B-cell proliferative disorder after chemotherapy in a patient with hemophagocytic lymphohistiocytosis with associated EBV-induced T-cell proliferation. 1104 20

Although it is well known that patients with type 1 diabetes mellitus are susceptible to other autoimmune diseases, the simultaneous occurrence of clustered distinct autoimmune diseases is uncommon. We report a 16-year-old girl, previously diagnosed as having coeliac disease and IgA deficiency, who at 13 years of age developed a clustering of distinct autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis (RA) and euthyroid autoimmune thyroiditis, eventually resulting in a simultaneous long-term remission. The clinical picture was associated with a functional immunodeficiency characterized by a defect in proliferative responses to T cell predominant mitogens and a normal response to the B cell predominant mitogen. In addition, the T cell activation markers HLA-DR, IL-2 receptor and transferrin receptor) were not upregulated. The clinical course of this immunodeficiency paralleled the outcome of the autoimmune diseases. After the abrupt onset, spontaneous clinical remission of both diabetes mellitus and RA was observed. Insulin was first reduced in dose and then discontinued completely at 15 months, in the presence of normal C peptide secretion and normal metabolic control (HbA1c 5.8%). Anti-glutamate decarboxylase (GAD65) and anti-IA-2 antibodies remained persistently high. During the remission phase a normalization of the functional immune defect was observed. The gradual resolution of the multisystemic diseases as well as the normalization of immune function in our patient is unusual. This case may be of considerable value in furthering our knowledge of the immunological mechanisms implicated in these rare multireactive syndromes.
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PMID:Simultaneous peripubertal onset of multireactive autoimmune diseases with an unusual long-lasting remission of type 1 diabetes mellitus. 1110 28

A vigorous expansion of antigen-specific CD8(+) T cells lacking apparent effector function was observed in a rhesus macaque acutely infected with the simian immunodeficiency virus (SIV) strain SIVmac239. Antigen-specific CD8(+) T cells were identified using antigenic-peptide class I major histocompatibility complex tetramers. As many as 8.3% of CD8(+) cells recognized the Mamu-A*01-associated SIV epitope Gag(181-189) (CTPYDINQM); however, these cells demonstrated no effector function when presented with peptide-incubated targets, as measured by intracellular cytokine staining for gamma interferon (IFN-gamma), interleukin-2 (IL-2) production, or direct cellular lysis. Similar results were observed with three other SIV peptide antigens. Nonresponsiveness did not correlate with apoptosis of the CD8(+) cells, nor were cells from this macaque impaired in their ability to present peptide antigens. Associated with the nonresponsive state was a lack of IL-2 production and decreased IL-2 receptor expression. Exogenous IL-2 treatment for 1 week in the absence of antigenic stimulation restored antigen-specific responses and the quantitative correlation between tetramer recognition and antigen-responsive IFN-gamma secretion. This case report suggests a regulatory mechanism that may impede the effector function of antigen-specific T cells during acute infection with SIV or human immunodeficiency virus in some cases. This mechanism may participate in the failure of the immune system to limit infection.
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PMID:Simian immunodeficiency virus (SIV) infection of a rhesus macaque induces SIV-specific CD8(+) T cells with a defect in effector function that is reversible on extended interleukin-2 incubation. 1122 30

Human immunodeficiency virus (HIV), the retrovirus associated with acquired immune deficiency syndrome (AIDS), induces a spectrum of immune abnormalities including a state of anergy in the host. This state is due to the binding of HIV envelope glycoprotein moieties to CD4 molecules and chemokine receptors. Resulting decrease in antigen presenting cell function and the interference with functioning of positive and negative regulatory molecules involved in signal transduction have an anergizing effect on the immune system. This effect is exemplified by diminished production of interleukin-2 (IL-2) and interferon-gamma and reduced expression of IL-2 receptor by CD4 helper cells of HIV patients. These immune abnormalities lead to clinically relevant immunological phenomena such as Type-1 to Type-2 switch, decrease in delayed-type hypersensitivity dermal reaction, etc. Insight into these interesting phenomena could pave the path for favorably altering the immunological milieu for drug and vaccine trials.
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PMID:Anergy and human immunodeficiency virus infection. 1135 64

Hematopoietic stem-cell transplantation is currently the most appropriate substitution therapy in the most severe forms of primary immunodeficiency diseases (all the variants of SCID, WA, CID etc.). It can achieve total and permanent immunological reconstitution in 60% of patients, depending on histocompatibility, source of the hematopoietic stem cells and the underlying disease. Stem-cell sources may be bone marrow, umbilical cord blood and the peripheral blood of donors previously treated with colony stimulating factors for the mobilization CD34. We discuss the differences in the results obtained in patients treated at the Hospital Materno-Infantil Vall d'Hebron. Gene therapy opens a new era in the treatment of primary immunodeficiency diseases. The first patient to undergo this treatment in the United States of America had adenosine-deaminase deficiency, even though sustained remodeling has not been achieved. The favorable results obtained in patients with SCID by deficit in the gamma chain of the IL-2 receptor in Paris, with more than a year of follow up, suggest that the near future is promising. We also discuss the differences observed according to the vectors used and the underlying disease.
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PMID:[Substitution therapy with hematopoietic progenitors in the primary immunodeficiencies]. 1143 85

The noncytotoxic soluble factor produced by CD8+ T cells inhibits replication of HIV and SIV in vitro and is thought to play a crucial role in combatting infection in vivo. We determined the effect of human CD8+ lymphocytes on the in vitro replication potential of both wild-type and nef-defective mutants of the simian immunodeficiency virus SIVmac251. Although replication of wild-type SIVmac251 in unstimulated human PBMC supplemented with IL-2 was unaffected by the presence of CD8+ T cells, the nef mutants were susceptible to the inhibitory effects. The effect of exogenous IL-2 depended upon the culture conditions: (i) in nonstimulated human PBMC depleted of CD8+ T cells, addition of IL-2 had a positive effect on the growth of the nef-defective viruses; (ii) in total human PBMC, IL-2 appeared to reinforce the CD8+ T-cell-dependent inhibition of the same mutant viruses. This strongly suggests that IL-2 stimulates the noncytotoxic anti-HIV/SIV response of CD8+ cells present in PBMC cultures. PHA stimulation of unfractionated human PBMC overrode the suppression of viral replication by CD8+ T cells. Depletion of activated T cells expressing the IL-2 receptor alpha-chain (CD25+ T cells), present in small amounts in these primary T cell cultures, dramatically reduced viral replication, indicating that the depleted cell population harbors the target cells permissive for viral replication. Furthermore, using neutralizing antibodies we could show that inhibition by the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES and the inhibitory effect of CD8+ lymphocytes on nef mutant SIVmac viruses are harbored on different levels.
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PMID:Simian immunodeficiency viruses with defective nef genes show increased susceptibility to the noncytotoxic antiviral activity of CD8+ lymphocytes. 1188 79

Human immunodeficiency virus (HIV) infection leads to a profound T cell dysfunction well before the clinical onset of acquired immunodeficiency syndrome (AIDS). We have been accumulating evidence that one of the mechanisms responsible for this T cell deficiency may be the dysregulation of signal transduction via the interleukin (IL)-2/IL-2 receptor (R) complex. In CD4 T cells, we have observed previously that viral envelope (env) glycoproteins induce IL-2 unresponsiveness and the down-regulation of the three chains making up the IL-2R (alpha, beta, gamma) in vitro. We have now established further that this disruption of the IL-2/IL-2R system manifests itself in defective signal propagation via the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathway in response to IL-2. The treatment of CD4 T cells with HIV env or surface ligation of CD4 with anti-CD4 monoclonal antibodies inhibited the IL-2-induced activation of Jak-1 and Jak-3, as well as their targets, STAT5a and STAT5b. This Jak/STAT deficiency may contribute to the crippling of CD4 T cell responses to a cytokine central to the immune response by HIV.
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PMID:Human immunodeficiency virus-1 envelope glycoproteins and anti-CD4 antibodies inhibit interleukin-2-induced Jak/STAT signalling in human CD4 T lymphocytes. 1260 94

Severe combined immunodeficiency (SCID) represents a genetically heterogeneous group of primary immunodeficiency disorders. Irrespective of the genetic defect, patients with SCID may be engrafted with transplacentally derived maternal T-lymphocytes that in a subset of cases may be responsive to phytohemagglutinin. Here, we present, from a genetic perspective, an SCID patient who not only harbored a novel mutation in the gene encoding the common gamma chain (gamma c) of the IL-2 receptor (IL2RG), but also carried reactive maternal T lymphocytes that produced a karyotype that was initially perplexing.
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PMID:A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a patient with severe combined immunodeficiency. 1660 12

This review comments on basic and clinical immunology articles that were published in 2005, with a focus on those that appeared in the Journal of Allergy and Clinical Immunology. In the area of basic immunology, mechanisms of the innate immune system and its interaction with the adaptive immune system were described, with special consideration to applications in biodefense strategies. T regulatory cells were further characterized in their role for the control of allergic, autoimmune, and neoplastic disorders. The function of the thymus Hassall's corpuscles was reported to be the generation of T regulatory cells. Flavonoid molecules obtained from medicinal herbs, including astilbin and epigallocatechin gallate, were discovered to have immunomodulatory properties. Advances in clinical immunology resulted from efforts to develop a newborn screening test for severe combined immunodeficiency and the elucidation of the crystal structure of the IL-2 receptor gamma chain. Mutations in the membrane receptor transmembrane activator and calcium modulator and cyclophilin ligand interactor were found in patients with common variable immunodeficiency. New therapeutic options are described, such as the use of infliximab for granulomas and GM-CSF for chronic ulcers in patients with common variable immunodeficiency. The importance of mucosal immunity in acute HIV infection is cited, as is the role of CD8+ T-cell activation in HIV disease progression in children.
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PMID:Advances in basic and clinical immunology. 1689 Jul 76


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