Disease relevance of IL2RA

• As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the biological candidate gene IL2RA (CD25), which encodes a subunit (IL-2R alpha) of the high-affinity interleukin-2 (IL-2) receptor complex [1].
• Unexpectedly, with the appropriate activation of the normal B cells by anti-mu antibody, phorbol myristate acetate, or Staphylococcus aureus Cowan I (SAC), Tac antigen was induced on the activated B cells [2].
• These results, taken together with those on normal IL-2 receptors on HTLV-I-negative T-CLL cells, suggest that abnormal expression of the IL-2 receptor in ATL is closely associated with HTLV-I infection and may play a role in the neoplastic growth of ATL cells [3].
• Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells [3].
• Northern analysis using a 32P-labeled cDNA probe for the IL 2R p55 protein demonstrated that blood T cells of patients with active sarcoidosis, but not of normal patients, express 3.5- and 1.5-kb IL 2R mRNA transcripts, the same as those observed in normal T cells activated in vitro [4].

Psychiatry related information on IL2RA

• In the 2 CD25 (Tac)- B-NHL patients serum Id levels were below the detection limit and the amount of Id+ Ig secreted in vitro did not surpass 50 ng/ml [5].
• After a night of sleep deprivation between 10 P.M. and 3 A.M., a reduction of natural immune responses as measured by NK cell activity, NK activity per number of NK cells, LAK activity, and LAK activity per number of LAK precursors (CD16,56, CD25) was found [6].
• High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder [7].
• We have previously demonstrated that soluble amyloid beta protein (A beta) induces IL-2 receptor expression and proliferation in peripheral T cells from young and old healthy individuals, but not from patients with Alzheimer's disease (AD) [8].
• Plasma levels of the sTNF-R p55, sTNF-R p75, and sIL-2R did not differ significantly between nocturnal sleep and nocturnal wakefulness [9].

High impact information on IL2RA

• Naturally occurring CD4+ regulatory T cells, the majority of which express CD25, are engaged in dominant control of self-reactive T cells, contributing to the maintenance of immunologic self-tolerance [10].
• Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit [11].
• Both the interleukin-2 receptor-alpha (Tac, p55, IL-2R alpha) gene and the long terminal repeat (LTR) of type 1 HIV are activated by various T cell mitogens [12].
• 5' deletion constructs extending to -327 directed CAT expression in HTLV-I-infected T cells, which express IL2R alpha constitutively, and in Jurkat cells, which express IL2R alpha only after induction [13].
• We have characterized regulatory regions of the human IL-2 receptor alpha chain (IL2R alpha) promoter [13].

Chemical compound and disease context of IL2RA

• 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 [14].
• These results reveal a selective blockade of the IL-2 cytokine axis distal to the IL-2 receptor by the L-778,123 and warrant evaluation of prenylation inhibitors in treating transplant rejection and autoimmune diseases [15].
• CD25, recognizing the p55 subunit of IL-2 receptor, was detected in all patients with aGVHD except two who, at the onset of eosinophilia, were already receiving methylprednisolone intravenously [16].
• The role of phorbol myristate acetate (PMA: a protein kinase-C (PKC) activator) and calcium ionophore A23187 in the induction mechanism of the interleukin 2 receptor (IL2R) on B-cell chronic lymphocytic leukemia (B-CLL) cells was studied [17].
• Inhibition of proliferation and CD25 down-regulation by retinoic acid in human adult T cell leukemia cells [18].

Biological context of IL2RA

• Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms [1].
• Gel retardation assays revealed that nuclear extracts from induced, but not uninduced, Jurkat and YT-1 cells mediated the formation of two specific DNA-protein complexes with oligonucleotides spanning the region of the IL2RA promoter from position -291 to -245, which contains two imperfect direct repeats (IDRs) [19].
• Furthermore, the IL15RA and IL2RA genes have a similar intron-exon organization and are closely linked in both human and murine genomes [20].
• The interleukin 2 receptor (IL2RA), a human Chromosome (Chr) 10p locus, was mapped to sheep Chr 13q12-q15 by in situ hybridization [21].
• Marsupial homologs of the human chromosome 10 loci IL2RA, HK1, and PLAU have been cloned and mapped by fluorescence in situ hybridization to chromosome 1q of the tammar wallaby, Macropus eugenii [22].

Anatomical context of IL2RA

• In further support of the biological significance of these DNA-protein interactions, the IL2RA oligonucleotide from -291 to -245 proved to be sufficient in either orientation to confer PMA inducibility to the mitogen-insensitive thymidine kinase gene promoter in Jurkat cells [19].
• A novel glycoprotein (IL-2R beta), identified on several lymphocytoid cell lines, has the ability to bind IL-2 alone and to associate with Tac antigen (IL-2R alpha) to form high-affinity IL-2 receptors [23].
• The expression of the murine interleukin (IL)-2 receptor alpha chain/CD25 is strongly induced at the transcriptional level after T cell activation [24].
• Detection and functional studies of p60-65 (Tac antigen) on activated human B cells [25].
• We investigated the effect of OKT3 antibody and interleukin 2 (IL-2) on Tac antigen expression and the proliferation of human peripheral blood mononuclear leukocytes [26].

Associations of IL2RA with chemical compounds

• Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression [27].
• No differences were noted between ATL cells and normal activated T cells in one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the IL-2 receptor [3].
• Tac antigen, the receptor for human interleukin 2 (IL-2), contains in its intracytoplasmic region a serine residue (Ser-247) that is seemingly the predominant site of protein kinase C-mediated phosphorylation [28].
• After 20 hr of culture, IL-2R mRNA was markedly decreased in both IL-2-toxin- and cycloheximide-treated phytohemagglutinin-activated T cells [29].
• Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone [30].

Physical interactions of IL2RA

• To distinguish the affinity conversion model and the binary complex model we have carried out kinetic studies on the IL-2 binding to the high affinity IL-2-R on T lymphocytes expressing various numbers of L chains and a relatively constant number of H chains [31].
• Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both [32].

Regulatory relationships of IL2RA

• Interleukin 2 regulates the expression of Tac antigen on peripheral blood T lymphocytes [26].
• IL-15 induced a significant T-cell proliferation and upregulated CD25 expression [33].
• Culture of human peripheral blood monocytes in vitro induces low level surface expression of the p55 protein of the IL-2R and the expression of this receptor can be enhanced significantly by exposure to IFN-gamma [34].
• This proliferative effect of TNF was inhibited by an anti-interleukin 2 receptor (IL2R) antibody, MAR 108, which blocks IL2 binding to its receptor [35].
• Such a small population of CD45RA+ CD4+ T cells expressing CD25 appeared to be present in the blood throughout human life [36].
• IL2RA has sense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding or non-coding RNAs with antisense Alu elements [37].

Other interactions of IL2RA

• The Tac antigen is an IL-2 binding protein of relative molecular mass 55,000 (Mr 55K) that participates in the formation of both high- and low-affinity receptors [38].
• Cell lines bearing either the p55 Tac or the p75 peptide alone manifested low-affinity IL-2 binding, whereas a cell line bearing both peptides manifested both high- and low-affinity receptors [39].
• We confirmed the physical proximity of p95/ICAM-1 to the IL-2 receptor alpha subunit by demonstrating that radiolabeled IL-2 could be cross-linked to this protein expressed on activated T cells [40].
• HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain [41].
• After a 6-day culture with or without Dermatophagoides farinae (Df) antigen, the expression of IL-2Rp55 (CD25) and p75 on CD4+ or CD8+ T lymphocytes was measured by flow cytometry [42].

Analytical, diagnostic and therapeutic context of IL2RA

• CONCLUSIONS: IL2RA immunotherapy after IT is associated with a lower incidence of renal dysfunction as compared with historical controls [43].
• Consistent with this, using flow cytometry and an MAb directed against the IL 2R p55 protein (2A3), we observed detectable levels of IL 2R surface protein on increased numbers of blood T cells of active sarcoidosis patients (4.7 +/- 0.9%) compared with blood T cells of normal patients (0.9 +/- 0.2%) [4].
• Expression of p55 (Tac/CD25) by eosinophils, without requirement for in vitro activation, was demonstrable by flow cytometry, radioimmunoprecipitation, and Northern blotting for mRNA [44].
• Consistent with these findings in cell culture, immunohistologic studies demonstrated p55 and p70 antigen in the vasculature of rheumatoid joints, but not in normal joint tissue [45].
• Combined immunoperoxidase staining and autoradiography of organ sections revealed that labelled IL2 bound specifically in vivo to IL2-receptor-positive cells in the spleen of both normal and BB/W rats and to activated lymphocytes infiltrating the pancreas of BB/W rats [46].

References