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 impact of the immunomodulatory photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) and visible light on the survival and surface receptor pattern of resting and activated murine T cells was evaluated. T cells treated for 48 h with immobilized anti-CD3 monoclonal antibody upregulated expression of the interleukin-2 receptor alpha-chain (CD25), transferrin receptor (CD71), the apoptosis-regulating Fas receptor (CD95), contained a greater level of the anti-apoptotic protein Bcl-2 and accumulated significantly more BPD-MA than their unactivated counterparts. Activated T cells displayed a modestly greater susceptibility to the photodynamic induction of DNA fragmentation than resting T cells. Resting T cells treated with sub-lethal levels of BPD-MA and light did not exhibit changes in surface levels of CD3, CD4, CD8, CD28, CD45 or T cell receptor (TCR) beta-chain structures. However, levels of major histocompatibility complex (MHC) class I antigens were decreased while the density of Thy-1.2 (CD90) increased on these cells. Photodynamically treated T cells failed to express optimal CD25 levels when exposed to the mitogenic anti-CD3 antibody. Activated T cells treated with sub-lethal levels of BPD-MA and light exhibited lower CD25 levels, a temporary block in cell cycle transition, but unaltered expression of MHC Class I, CD3, CD4, CD8, CD45, CD54, CD71, CD122 (IL-2R beta-chain) or TCR beta-chain antigens 24 h afterward. Resting and activated T lymphocytes differ in susceptibility to PDT-mediated apoptosis but both types are sensitive to anti-proliferative effects the treatment exerts at sub-lethal photosensitizer levels. The marked sensitivity of activated T cells to photodynamic inactivation likely contributes to the immunomodulatory action of BPD-MA.
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PMID:Consequences of the photodynamic treatment of resting and activated peripheral T lymphocytes. 995 Feb 67

One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers.
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PMID:The prognostic significance in HIV infection of immune activation represented by cell surface antigen and plasma activation marker changes. 1008 Aug 36

The costimulatory molecule CD28 is expressed on almost all CD4+ T cells, but on only a portion of CD8+ T cells in healthy human adults. alpha beta T cells may thus be divided into three phenotypically and functionally different subsets: CD4+, CD8+CD28+ and CD8+CD28-. Using peripheral blood lymphocytes from six healthy adults, we have studied the T cell receptor (TCR) repertoire within these subsets by analysis of the distribution of lengths of the complementarity determining region 3 (CDR3) of the beta variable (BV) transcripts and flow cytometric analysis of TCR V beta usage. Expanded CDR3 lengths were identified in 86% of BV families within CD8+CD28- T cells, but in only 4% within CD4+ T cells, and 35% within CD8+CD28+ T cells (P < 0.01). When sequenced, the majority of expanded peaks were found to be dominated by single clones. Identical expanded clones were found within both CD8+CD28+ and CD8+CD28- subsets, consistent with the belief that CD8+CD28- T cells descend directly from CD8+CD28+ T cells. Greatly expanded CD28- clones were found within both CD8+ and CD4+ subsets and persisted at the same magnitude for up to 4.5 years of observation. The finding of a small proportion of cells expressing Ki-67 showed that some of these clonally expanded cells were in the active stages of the cell cycle, but few of the cells expressed activation markers CD69, CD25, CD71 or CD122. One likely explanation for the persistence of expanded peripheral lymphocyte populations in healthy individuals is the presence of persistent antigen.
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PMID:The T cell receptor repertoire of CD8+CD28- T lymphocytes is dominated by expanded clones that persist over time. 1044 61

Clinical impact of s.c. administration of IL-2 and/or IFN alpha was studied in 23 pediatric patients with Hodgkin lymphoma (IFN alpha group) and sarcoma, non-Hodgkin lymphoma, peripheral neuroepitelioma, neuroblastoma, and embryonic carcinoma (IL-2 + IFN alpha group) after autologous PBSC transplantation. Expression of CD3, CD4, CD8, CD25, CD38, CD56, CD71, CD122, and HLA-DR antigens, serum level of the soluble IL-2R alpha, and NK activity against K562 cell line were evaluated in 11 patients representative for both types of immunotherapy. T and, more markedly, NK cell proliferation, induction of activation markers on the surface of T and NK subsets, and elevation of sIL-2R alpha concentrations were seen in the IL-2 + IFN alpha subgroup. In the IFN alpha subgroup, the total number of lymphocytes and expression of activation markers remained unchanged, but the number of CD8+ T cells increased at the expense of CD4+ T and NK cells during the therapy. Cytotoxic activity against K562 cells was not influenced by the immunotherapy in either subgroup. No significant clinical benefit of the immunotherapy was seen in these patients compared to 27 control patients with relevant diagnoses who did not receive immunotherapy.
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PMID:Clinical ineffectiveness of IL-2 and/or IFN alpha administration after autologous PBSC transplantation in pediatric oncological patients. 1068 13

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator gene and characteristically leads to prominent lung and pancreatic malfunctions. Although an inflammatory reaction is normally observed in the CF airways, no studies have been performed to establish whether a chronic inflammatory response is also present in the CF intestine. We have investigated whether immunologic alterations and signs of inflammation are observed in CF small intestine. Fourteen CF, 20 negative, and four disease controls underwent duodenal endoscopy for diagnostic purposes. Two CF patients were rebiopsied, one after 3 mo of an elemental diet and the other after 2 wk of pancreatic enzyme withdrawal. In three CF and 10 controls, in vitro small intestine organ cultures were also performed. Expression of ICAM-1, IL-2 receptor, IL-2, IFN-gamma, CD80, and transferrin receptor was studied by immunohistochemistry before and after in vitro organ culture. In CF small intestine, an increased number of lamina propria mononuclear cells express ICAM-1 [mean 114 (SD 82.8), p < 0.001 versus controls], CD25 [20.2 (18.7), p < 0.01], IL-2 [23.6 (13.7), p < 0.05], and IFN-gamma [19 (15.9), p < 0.05], whereas villus enterocytes highly express transferrin receptor. Reduced expression of immunologic markers was observed after 24 h of in vitro culture in all three CF patients as well as in the patient kept on elemental diet for 3 mo. These results indicate that chronic inflammation is observed in CF duodenum and suggest that the perturbation of local mucosal immune response may contribute to the overall clinical picture in CF patients.
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PMID:Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients. 1070 33

Immunogold staining and electron microscopy show that IL-2 receptor alpha-subunits exhibit nonrandom surface distribution on human T lymphoma cells. Analysis of interparticle distances reveals that this clustering on the scale of a few hundred nanometers is independent of the presence of IL-2 and of the expression of the IL-2R beta-subunit. Clustering of IL-2Ralpha is confirmed by confocal microscopy, yielding the same average cluster size, approximately 600-800 nm, as electron microscopy. HLA class I and II and CD48 molecules also form clusters of the same size. Disruption of cholesterol-rich lipid rafts with filipin or depletion of membrane cholesterol with methyl-beta-cyclodextrin results in the blurring of cluster boundaries and an apparent dispersion of clusters for all four proteins. Interestingly, the transferrin receptor, which is thought to be located outside lipid rafts, exhibits clusters that are only 300 nm in size and are less affected by modifying the membrane cholesterol content. Furthermore, transferrin receptor clusters hardly colocalize with IL-2Ralpha, HLA, and CD48 molecules (crosscorrelation coefficient is 0.05), whereas IL-2Ralpha colocalizes with both HLA and CD48 (crosscorrelation coefficient is between 0.37 and 0.46). This coclustering is confirmed by electron microscopy. The submicron clusters of IL-2Ralpha chains and their coclustering with HLA and CD48, presumably associated with lipid rafts, could underlie the efficiency of signaling in lymphoid cells.
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PMID:Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts. 1082 48

This study shows that naive CD8 T cells can acquire characteristics of memory T cells in the absence of stimulation with specific Ag simply by the process of homeostatic proliferation under lymphopenic conditions. This Ag-independent T cell differentiation pathway did not result in up-regulation of early activation markers (CD69, CD25, CD71), but expression of several memory markers (CD44, CD122, Ly6C) increased progressively with successive divisions. These markers were then stably expressed, and these cells also became more responsive functionally to specific Ag. Thus, all "memory" phenotype T cells in an individual may not be true Ag-experienced cells and may include naive cells masquerading as memory cells. These findings are specially relevant in cases of disease or treatment-induced lymphopenia such as in HIV-infected individuals or transplant recipients. In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules.
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PMID:Cutting edge: naive T cells masquerading as memory cells. 1092 49

Owing to the contrasting observations in the field of interleukin(IL)-2 receptor research, the expression of IL-2 receptor chains was analysed on resting and anti-CD3 antibody (OKT3) activated CD4 and CD8 T cells by flow cytometry. Prior to the stimulation, 49% of CD4+ cells expressed IL-2Ralpha (CD25), whereas the expression of IL-2Rbeta (CD122) was very low (8%). The reverse was true for CD8 cells: 48% of them were positive for CD122, but only a fraction (10%) expressed CD25. Practically all lymphocytes expressed IL-2Rgamma (CD132). Interestingly, the unbalanced expression of IL-2Ralpha and -beta continued throughout the stimulation period of 2 days. In addition, the expression of CD45 isoforms in combination with the IL-2R chains and CD71 was followed during the activation of CD4+ T cells. Although CD45RA+/RO- CD4 cells were effectively activated, they retained their naive phenotype up to 2 days of stimulation. On the other hand, CD45RA+low/RO+low (Ddull) CD4+ cells shifted to the memory phenotype rapidly after being activated. However, by day 6 of stimulation the shift of both naive and Ddull cells to memory ones was obvious. The role of the IL-2 receptor in the activation of CD4 subpopulations is discussed.
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PMID:T-lymphocyte subpopulations do not express identical combinations of interleukin-2 receptor chains in the early phase of their activation and proliferation. 1093 79

Our previous work examining the importance of insulin receptor (IR) expression on T cells has demonstrated that when T cells from nonobese diabetic mice were sorted into populations expressing a high (IR(High)) and a low (IR(Low)) density of IR, IR(High) T cells rapidly transferred insulitis and diabetes. We have further characterized IR(High) T cells. Both CD4+ and CD8+ cells were detected in the IR(High) T cell population, but IR(High) expression was detected predominantly on CD4+ cells. IRHigh T cells were polyclonal for TCR Vbeta-chain expression. By 3 color flow cytometric analysis, virtually all IR(High) T cells expressed low or negligible levels of CD62L (CD62L(Low)/-) and high levels of CD44 (CD44(High)). The lack of IL-2 receptor and transferrin receptor expression as seen previously, together with the CD62L(Low)/- CD44(High) phenotype suggests that IR(High) T cells are memory cells. However, since only about one quarter of all of the CD62L(Low)/- or CD44(High) T cells were also IR(High), the IR(High) phenotype defines a subpopulation of memory T cells that are aggressively diabetogenic.
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PMID:High density insulin receptor-positive diabetogenic T lymphocytes in nonobese diabetic mice are memory cells. 1095 38

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


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