Disease relevance of IL2RB

• Binding of monoclonal antibody against p75 was not detectable by flow cytometry, and high affinity binding sites for 125I-IL-2 were below the limits of quantitation on eosinophils from individuals with eosinophilia [1].
• Unlike hairy cells, only 8 of the 15 B-cell chronic lymphocytic leukemia cases tested showed a weak expression of the p75 antigen on a small proportion of cells [2].
• Monoclonal antibodies against the alpha-chain (p55) of the human IL-2 receptor are being applied to prevent transplant rejection and graft-versus-host disease in several clinical trials [3].
• The present data suggest that IL-2R/p75 expression is involved in the host immune response triggered by the rubella virus [4].
• The expression of the p75 subunit of interleukin 2 receptor in Tac negative leukemic cells of two patients with large granular lymphocytic leukemia [5].

Psychiatry related information on IL2RB

• Freshly drawn cells from 3 out of 5 patients expressed the IL-2 receptor (CD25; Tac antigen) or acquired this marker during culture in vitro and secreted relatively high levels of Id+ Ig in vitro [6].
• Does the p75 neurotrophin receptor mediate Abeta-induced toxicity in Alzheimer's disease [7]?

High impact information on IL2RB

• Cells expressing a noncleavable mutant of p75 sustain DeltaPsim and ATP levels during apoptosis, and ROS production in response to apoptotic stimuli is dampened [8].
• While cytochrome c release and DNA fragmentation are unaffected by the noncleavable p75 mutant, mitochondrial morphology of dying cells is maintained, and loss of plasma membrane integrity is delayed [8].
• Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain [8].
• Many investigations indicate that the survival-promoting signals of neurotrophins are generated by activation of Trk tyrosine kinase receptors and that their death-promoting signals are generated by activation of p75 neurotrophin receptors (p75(NTR)) [9].
• 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 [10].

Chemical compound and disease context of IL2RB

• MATERIAL/METHODS: The plasma levels of TNFalpha, its soluble receptor p75 (sTNF-RII), IL-6, and the soluble IL-6 receptor (sIL-6R) were measured using ELISA in 17 patients with ANCA-positive renal vasculitis (12 active - ANCA-A, 7 in remission ANCA-R), 9 patients with active lupus nephritis (LN), and 5 healthy subjects [11].
• Recently, the genetic defect responsible for X-linked SCID has been identified as a mutation in the gamma chain of the IL-2 receptor, a protein also shared by the IL-4 and IL-7 receptors and therefore now denoted the common gamma chain (gamma c) [12].
• Penta-acetyl geniposide induce apoptosis in C6 glioma cells by modulating the activation of neutral sphingomyelinase-induced p75 nerve growth factor receptor and protein kinase Cdelta pathway [13].
• Exposure of SN56 cholinergic neuroblastoma cells to dibutyryl cAMP and retinoic acid for 3 days caused their morphologic differentiation along with the increase in choline acetyltransferase activity, acetylcholine content and release, calcium content, and the expression of p75 neurotrophin receptors [14].
• Two borderline abnormal sweat chloride tests together with isolation of Pseudomonas from the airway caused clinicians initially to suspect CF; however, mutation in gene coding for the gamma-chain of the IL-2 receptor and a negative CF genetic mutation analysis ultimately led to the final diagnosis of SCID [15].

Biological context of IL2RB

• Linkage between seven markers spanning chromosome 22 spaced approximately 10 cM apart (D22S264, D22S274, D22S301, D22S304, D22S421, IL2RB, and PDGFB) and VO2max at baseline, as well as its response to endurance exercise training, was examined using the sib-pair linkage method [16].
• Patients with cancers of a histology previously reported to express the p55 component of the IL-2 receptor and who could not receive potentially more effective therapy were eligible for enrollment [17].
• The role of IL-2 interaction with p75 and p55 receptor molecules in the stimulation of cell proliferation [18].
• Mechanistic studies of transforming growth factor-beta inhibition of IL-2-dependent activation of CD3- large granular lymphocyte functions. Regulation of IL-2R beta (p75) signal transduction [19].
• In the present study, using the pre-B cell line Baf-B03 transfected with a truncated form of the IL-2 receptor (IL-2R) beta chain, we demonstrate that IL-2-dependent cell survival requires only the N-terminal 350 amino acids of the IL-2Rbeta chain [20].

Anatomical context of IL2RB

• 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 [21].
• Furthermore, fusion of cell membranes from low-affinity IL-2 binding cell lines bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generated hybrid membranes bearing high-affinity receptors [21].
• In vitro studies demonstrated that the retinoid X receptor (RXR) retinoid, bexarotene, at biologically relevant concentrations of 10(-6) M to 10(-8) M, upregulated both the p55 and p75 subunits of the IL-2R and enhanced 5- to 10-fold the susceptibility of T-cell leukemia cells to denileukin diftitox [22].
• This was in contrast to the partial inhibition of proliferation by anti-p75 or anti-TAC observed in unstimulated pretherapy peripheral blood lymphocytes suggesting that these cells respond to IL-2 through both high affinity receptors and intermediate affinity p75 receptors [23].
• In this study, we present data indicating that NK cells activated by in vivo IL-2 treatment, in contrast to resting NK cells, respond and proliferate to further IL-2 in vitro using primarily the p75 receptor with only a minor component of cells responding through the high affinity receptor [23].

Associations of IL2RB with chemical compounds

• The effect of DM on expression of IL-2R alpha (Tac, p55, CD25) and beta (p75) genes in activated T cells was examined next [24].
• Lipopolysaccharide (LPS) upregulates expression of p75 and effectively induces surface expression of CD25 on human monocytes within 18 h, as detected by two-colour FACS analysis on 59.5 +/- 7.6% of cells [25].
• Incubation of CD19+ cells with 10 ng/mL of TNF increased the incorporation of thymidine in 11 patients tested, and this was decreased to 65% (P < .05) by antibodies to the p55 receptor or the p75 receptor, and to 35% +/- 7% (P < .001) when both antibodies were combined [26].
• Nevertheless, IL-2 stimulates the activation of one or more tyrosine kinases requiring the functional participation of the p75 member of the receptor complex [27].
• Anti-CD3 antibody-induced expression of both p55 and p75 chains of the high affinity interleukin-2 receptor on human T lymphocytes is inhibited by cyclosporin A [28].

Physical interactions of IL2RB

• Fusion of cell membranes from low-affinity IL-2 binding cells bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generates hybrid membranes bearing high-affinity receptors [29].
• A second sequence element located 3' to the NF-kappa B-binding site regulates IL-2 receptor-alpha gene induction [30].

Regulatory relationships of IL2RB

• However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population [31].
• In healthy controls, 0% to 1% of the CD19+ cells expressed the p55 receptor and 0% to 10% expressed the p75 receptor [26].
• IL-18 up-regulated IL-2 receptor expression in mucosal lymphocytes from patients with CD, but not from normal controls [32].

Other interactions of IL2RB

• Expression on cells of early human pregnancy decidua, of the p75, IL-2 and p145, IL-4 receptor proteins [33].
• In lymph nodes and other secondary lymphoid tissues, the p75 receptor was expressed on activated lymphocytes and interdigitating reticulum cells of the T cell areas, whereas the p55 receptor was confined to the germinal center dendritic reticulum cells, which are the main site of TNF-alpha production [34].
• AGC10 also decreased the intracellular levels of CD25, CD122, and CD132 in CD4(+) and CD8(+) cells stimulated with the T-cell mitogen phytohemagglutinin (PHA) [35].
• In contrast, p75 alone is capable of mediating the production of GM-CSF [36].
• However, in contrast to the other two groups, in recipients of T cell-depleted BMT the majority of these cells co-expressed p75 chain and CD56 antigen [37].

Analytical, diagnostic and therapeutic context of IL2RB

• Whilst B cells in human blood can be shown to express interleukin-2 receptor (IL-2R) p55 and p75 chains, using a high-sensitivity immunofluorescence procedure, fresh tonsil B cells did not show detectable levels of expression [38].
• Expression of p75 chain of IL-2 receptor in the early immunological reconstitution after allogeneic bone marrow transplantation [37].
• The nature and location of cells responding to tumor necrosis factor-alpha were investigated in situ by immunohistochemistry using monoclonal antibodies directed against the p75 and p55 proteins of the TNF receptor [34].
• The distribution of type I (p55) and type II (p75) tumor necrosis factor receptors (TNF-Rs) in human polymorphonuclear neutrophils (PMNs) was analyzed by Western blotting of subcellular fractions obtained by centrifugation of PMN cavitates on Percoll density gradients [39].
• The 75 kd molecule was identical to p75 detected by TU27 mAb specific for human IL-2Rp75 in sequential immunoprecipitation [40].

References