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)

Nickel is the major cause of metal-induced allergic dermatitis. Twelve nickel-specific T cell clones were used to investigate the cellular immune reactions occurring in nickel sensitivity. The selection between the alternative T cell receptors alpha beta and gamma delta and two alternative V beta genes (V beta 5 and V beta 8) were studied to see if nickel induces a selective pressure for clones bearing particular genes. Cell surface markers were studied by monoclonal antibodies and flow cytometry. Soluble mediators were measured by an ELISA method. The clones used T cell receptor alpha beta genes but did not use V beta 5 or V beta 8. They were T helper clones with a primed memory marker (CD3+ CD4+ CD8- CD45RO+) and carried HLA-DR. None of the clones secreted IL-1 alpha, all of them secreted IL-2 receptor. Four clones secreted IL-1 beta, six IL-4 and seven IL-6, the peaks in IL-2R and IL-6 secretion preceding IL-4 secretion. The clones helped immunoglobulin synthesis. The clones from late effector phase of the nickel allergic reaction favours the use of T cell receptors alpha beta genes. Nickel-specific clones were phenotypically indistinguishable but differed in soluble mediators produced.
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PMID:Characterization of nickel-specific T cell clones. 182 95

Nickel sulphate antigen-induced peripheral blood lymphocyte activation in vitro was characterized by lymphokine measurement (IL-2, IFN-gamma) and phenotyping of the IL-2 responsive cells. Mononuclear cells from nickel-sensitive patients synthesized more DNA, produced more IL-2 and had more IL-2 receptor positive cells in response to nickel than did those of the control subjects. On the other hand no IFN-gamma was detectable in the nickel supernatants, while PPD, used as the control antigen, induced pronounced quantities of IFN-gamma with an equal amount of DNA synthesis. The increase in IL-2 receptor positive cells was due to activation of CD4+ (helper/inducer) T cells. T cells with HLA-DR antigen surface markers were more numerous on each day of culture than cells with IL-2 receptors. These two activation markers were co-expressed on the same cells only to a certain extent, thus perhaps reflecting different types or phases of activation. In conclusion, nickel-induced peripheral blood mononuclear cell activation in vitro differs from microbial antigen-induced activation with respect to its modest or non-existent IFN-gamma response.
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PMID:Nickel antigen induces IL-2 secretion and IL-2 receptor expression mainly on CD4+ T cells, but no measurable gamma interferon secretion in peripheral blood mononuclear cell cultures in delayed type hypersensitivity to nickel. 297 21

Four out of eighteen (22%) patients with nickel contact sensitivity showed inhibition of skin patch test responses to the allergen in the presence of topical cyclosporin A (CsA; 5% v/v). No systemic drug absorption or side effects were detected. The clinical response to CsA was accompanied by marked diminution of the T cell infiltrate, although no alteration in the helper/suppressor cell ratio was observed. Expression of the Leu 6 marker on epidermal Langerhans cells and of major histocompatibility complex (MHC) class II antigens (HLA-DR, DQ and DP) on lymphocytes and Langerhans cells was unaffected by topical CsA. The incidence of IL-2 receptor positive lymphocytes in all biopsies was too small to ascertain the influence, if any, of CsA. The prospective use and method of application of CsA in immune contact dermatitis and other immunologically-based skin disorders warrants further evaluation.
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PMID:Topical cyclosporin A in nickel contact hypersensitivity: results of a preliminary clinical and immunohistochemical investigation. 355 35

We previously showed the median duration of positive patch test reactions to nickel sulfate (5% pet.) was 9 days, and defined as long-lasting (LLAPTR) the 14.3% of reactions that persisted for 17 days or longer. The pathomechanisms of LLAPTR are unclear, but may involve either localized antigen persistence or abnormal downregulation of the cellular immune response. In this study, we compared (a) the nickel concentration and (b) the immunocytochemical nature of the local immune reaction, between biopsies from LLAPTR (n = 8) and normally resolving allergic patch test reactions (NRAPTR) (n = 8) to nickel sulfate. The concentration of nickel in LLAPTR (median 0.56 microgram/g, range 0.25-3.87 micrograms/g, mean 0.83 microgram/g, 95% CI 0.35-1.31) and NRAPTR (median 0.58 microgram/g, range 0.2-1.85 micrograms/g, mean 0.88 microgram/g, 95% CI 0.02-1.74) was similar. Activated T lymphocytes, expressing surface IL-2 receptor, HLA DR, DR alpha 1, DP, DQ, and CD2 > CD8 > CD4 antigens, were seen throughout the dermis and occasionally infiltrating the suprabasal layer of the epidermis in all biopsies. CD1 and HLA DR, DR alpha 1, DP, and DQ-expressing Langerhans cells were present throughout the epidermis and occasionally seen in the papillary dermis. HLA DR, DR alpha 1, DP, and DQ antigen expression were also seen on the surface of non-dendritic cells in the epidermis (probably either keratinocytes or T lymphocytes) and vascular endothelial cells in the papillary dermis. There were no significant qualitative or quantitative differences in the immunocytochemical nature of the localized immune reaction between LLAPTR and NRAPTR. These findings suggest that the pathomechanism of LLAPTR to nickel sulfate is unlikely to be explained simply on the basis of nickel concentration or the nature of the localized immune reaction at the patch test site.
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PMID:Long-lasting allergic patch test reactions to nickel sulfate: analysis by nickel quantification and immunocytochemistry. 868 35

The data of a closed phase I/II trial in patients with resistant Hodgkin's lymphoma indicate promising results using a chemically linked anti-CD25 ricin-A immunotoxin (IT) (RFT5-SMPT-dgA). This IT is based on the high-affinity moab RFT5. Since recombinant DNA technology permits the readier production of large amounts of ITs, we constructed a new RFT5-based fusion toxin [RFT5(scFv)-ETA']. We isolated mRNA from the hybridoma cell line RFT5, synthesized first strand cDNA and performed RT-PCR. Amplified coding regions of the light and heavy chain variable domains were joined together with a synthetic (Gly4-Ser)3 linker. The resulting single chain variable fragment (scFv) was fused to a modified Pseudomonas aeruginosa exotoxin A (ETA') lacking its cell-binding domain I. After IPTG-induced expression in Escherichia coli, the 70 kDa His-tagged fusion protein [RFT5(scFv)-ETA'] was isolated by osmotic shock and sonication under denaturing conditions. The recombinant toxin was purified on a Ni2+-NTA chelating sepharose and eluted with 250 mM imidazole. Pooled protein was renatured, dialyzed and concentrated by precipitation. Binding properties of RFT5(scFv)-ETA' were assessed on the CD25-expressing cell line L540cy by ELISA, immunohistochemistry and FACS analysis. CD25-specific binding was confirmed by immunoprecipitation experiments with recombinant human IL-2 receptor alpha. The in vitro toxicity of the chimeric protein was tested on the Hodgkin-derived cell lines L540cy, L428, L1236, a monocyte cell line U937 and a Burkitt lymphoma cell line BL38. RFT5(scFv)-ETA' inhibited protein biosynthesis of L540cy and L428 cells by 50% at concentrations (IC50) of 18 and 12 ng/ml, respectively. CD25-specific toxicity was confirmed by competitive toxicity assays. These data confirm for the first time binding specificity and toxicity of a recombinant anti-CD25 immunotoxin, against Hodgkin-derived cell lines; its applicability on Hodgkin's lymphoma needs yet to be evaluated in vivo.
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PMID:Construction and in vitro evaluation of RFT5(scFv)-ETA', a new recombinant single-chain immunotoxin with specific cytotoxicity toward CD25+ Hodgkin-derived cell lines. 985 27