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)

T-cell-enriched populations obtained from lymph nodes (LNs) of 4-month-old MRL/Mp-lpr/lpr (MRL-lpr), C3H/HeJ-lpr/lpr (C3H-lpr), and C3H/HeJ-gld/gld (C3H-gld) mice were studied for the expression of B220, L3T4, and Lyt 2 antigens. A new B220+ L3T4+ phenotype was demonstrated in T-cell populations of these mice by two-color flow cytometry with phycoerythrin-conjugated monoclonal antibodies (MoAb) to L3T4 and FITC-anti-B220 MoAb. The generation of the T subset was apparently under the influence of the lpr or gld gene, since it could not be demonstrated in T-cell-enriched populations of MRL/Mp- +/+ and normal C3H mice. The expression level of L3T4 antigen on the T subset was lower than that on B220- L3T4+ cells, while the level of B220 antigen was similar to that of B220+ L3T4- or B220+ Lyt 2- cells. The B220+ L3T4+ phenotype appeared in LNs and spleens, but not in thymuses, of MRL-lpr mice as early as 2 months of age. Its proportion to whole LN T cells at this age was equivalent to that observed in 4-month-old mice. Functional studies on FACS-sorted cell populations revealed that the T subset similar to B220+ L3T4- cells possessed deficiencies in the IL-2-IL-2 receptor system. The appearance of the T subset with an intermediate phenotype and its functional defects suggests that lpr and gld genes in these autoimmune mice exert their influences on the ontogeny and function of L3T4+ T cells and contribute to the induction of early lupus.
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PMID:Ontogeny and function of B220+ L3T4+ T-cell subset of MRL/Mp-lpr/lpr mice. 245 58

Our results provide important evidence that IL-2 receptor bearing cells are required for undesired immune reactions involved in autoimmunity, allograft rejection and nephritogenic processes. Administration of anti-IL-2 receptor monoclonal antibodies prolonged vascularized heart allograft survival across major histocompatibility barrier in mice and rats and renal monkey grafts. Indeed, several grafts survived indefinitely, although the antibody was administered only for the first 10 days post-transplantation. Rejection of the remaining grafts may well reflect inadequate dosage of antibody; dose-response studies have not been performed to date. In addition to preventing rejection, delayed treatment with anti-IL-2R monoclonal antibody was shown to reverse ongoing rejection in other recipients of heart allografts. Such long-term engraftment following cessation of therapy makes it unlikely that anti-IL-2R treatment prolongs graft survival by pharmacologic blockade of the IL-2R. Furthermore, exogenous IL-2 does not diminish the beneficial effects of anti-IL-2R antibody therapy in rodents. Whether or not such prolonged graft survival represents deletion of the responding T cell clones is a subject of current investigation. Results in a delayed-type hypersensitivity model indicate that complement fixation, is required to achieve optimal immunosuppression. Moreover, only anti-receptor antibodies that block IL-2 binding mediate optimal immunosuppression. Passive transfer experiments clearly prove that immediate post-transplant courses of anti-IL-2R monoclonal antibody spares suppressor T cells. In rodent models, delayed type hypersensitivity and lupus and diabetic autoimmunity are prevented by anti-IL-2R treatment. Finally, the availability of monoclonal antibodies directed against the human IL-2R provides an opportunity to extend this principle to clinical transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toward more selective therapies to block undesired immune responses. 265 66

Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon gamma (IFN gamma) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (less than 24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN gamma mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFN gamma) may be of importance. The elevation of IFN gamma mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected.
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PMID:Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interleukin-2 (IL-2) IL-2 receptor and IFN-gamma. 312 92

The mRNA expression of interleukin (IL)-2, IL-2 receptor-alpha-chain (IL-2R alpha), IL-4 and interferon-gamma (IFN-gamma) in spleen cells from NZB/NZW F1) mice following the stimulation with concanavalin A (Con A) was examined by Northern blot analysis. Kinetic patterns of the mRNA expression after the stimulation were not different between 2-month-old and 6 to 8-month-old B/W F1 mice. However, relative mRNA expression of IL-2 to a cytoskeletal protein, alpha-Tubulin was lower in 6 to 8-month-old B/W F1 mice than in 2-month-old mice. Similar but not significant tendency was observed in IL-2R mRNA expression. In contrast, Relative IL-4 mRNA expression in 6 to 8-month-old B/W F1 mice was significantly higher than that in 2-month-old animals. On the other hand, no apparent change was observed in IFN-gamma mRNA expression. Flow cytometric analysis indicated that there was no apparent difference in proportion of L3T4 positive T cells in spleen cells from 2 and 6 to 8-month-old B/W F1 mice. These results suggest that mRNA expression of IL-2 and IL-4 differentially changes with aging in autoimmune B/W F1 mice.
Lupus 1995 Jun
PMID:Age-related differential mRNA expression of T cell cytokines in NZB/NZW F1 mice. 765 92

Subacute cutaneous lupus erythematosus (SCLE) is a subset of lupus erythematosus which is characterized by unique cutaneous manifestations and immunological abnormalities. Soluble IL-2 receptor (sIL-2 R) is the shed product of membrane Il-2 R, a product of T cell activation. It is measured by enzyme-linked immunosorbent assay (ELISA) and has been found to correlate well with disease activity in systemic lupus erythematosus (SLE) patients. The objective of the present work was to determine whether there is a correlation between sIL-2 R levels and disease activity in SCLE. Serum samples were obtained from 25 SCLE patients and then measured for sIL-2 R levels of ELISA. Fifteen of 25 SCLE patients tested had normal levels of sIL-2 R, while 10 of 25 SCLE patients had elevated sIL-2 R levels. The serum sIL-2 R level in SCLE patients correlated well with disease activity and the number of American College of Rheumatology criteria for SLE. These findings indicate that sIL-2 R levels can be used as a valuable laboratory parameter in managing SCLE patients.
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PMID:Elevated serum soluble interleukin-2 receptor levels in subacute cutaneous lupus erythematosus. 769 47

Cell surface expression of lysosome-associated membrane proteins (LAMPs) correlates with serum interleukin-8 (IL-8) levels, shorter disease duration, greater functional impairment from disease-related symptoms and soluble IL-2 receptor levels (sIL-2R) in patients with scleroderma. In this study of 46 patients with systemic lupus erythematosus (SLE), the relationship of serum IL-8 and cell surface LAMP to two clinical measures of disease activity, the SLEDAI and SLAM scales, was evaluated. IL-8 levels were determined on serum samples by the immunometric sandwich enzyme immunoassay technique. Cell surface LAMP expression was determined by flow cytometric quantitation of peripheral blood mononuclear cells with monoclonal antibodies directed against two of the major LAMP proteins, lamp1 and lamp2. The clinical disease activity scales correlated significantly with each other, with C3 levels, serum IL-8, C4, dsDNA and sIL-2R. Lamp1 and lamp2 expression correlated with the SLAM but not the SLEDAI scale. Serum IL-8 levels were elevated in 49 of 51 samples tested (44 of 46 patients) and had a stronger correlation with disease activity than C4, dsDNA and sIL-2R levels. Significantly higher levels of IL-8 were seen in patients with evidence of renal involvement. Serum IL-8 and cell surface LAMP expression may be useful indicators of disease activity in patients with SLE. The possible role of IL-8 in the pathogenesis of SLE requires further investigation.
Lupus 1994 Apr
PMID:Correlation of serum interleukin-8 and cell surface lysosome-associated membrane protein expression with clinical disease activity in systemic lupus erythematosus. 792 Jun 21

Splenic T-cells from lupus strain (NZB/W F1, Mrl/lpr) mice lack the ability to respond to concanavalin A (Con A) by secretion of IL-2 and hence expression of IL-2 receptor and proliferation. These defects were found not only in an aged group (> 5 months) of mice in which obvious clinical 'SLE like' symptoms and elevated levels of serum autoantibodies were observed, but also in mice as young as 4-wk. We demonstrate here that the defective mitogenic activation of T-cells from lupus mice is due to the inability of T-helper cells to produce IL-2 and this defect can be restored by exogenous IL-2 in vitro. Con A-induced cell proliferation and IL-2 receptor expression on CD3+ cells from lupus mice occur only in the presence of exogenous IL-2, whereas normal T-cells from BALB/c and CBA control mice are activated by the mitogen and undergo complete cell cycling in the absence of exogenous IL-2, as they are able to secrete sufficient endogenous IL-2. The detection of impaired T-helper function in young lupus mice, before development of overt disease, and the reversible nature of the defect indicate that defective IL-2 activity may be fundamental to the mechanism of development of pathology in SLE.
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PMID:Restoration of an early, progressive defect in responsiveness to T-cell activation in lupus mice by exogenous IL-2. 821 27

The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were determined in an attempt to relate these parameters with disease activity in systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE patients were significantly higher than those of the control group (P < 0.05) while CD25+ expression was similar in both groups. Only sIL-2R levels were significantly higher (P < 0.05) in active than in inactive patients.
Lupus 1993 Aug
PMID:Relationship of IL-2, IL-2R (CD25+), soluble IL-2R and IL-4 with disease activity in SLE patients. 826 74

Studies from our laboratory indicate that n-3 (fish oil, FO) lipids at 10% (w/w) in a nutritionally adequate, semipurified diet, and supplemented with equal levels of antioxidants, extended the life span of lupus-prone (NZB/NZW)F1 (B/W) female mice as compared to n-6 (corn oil, CO) lipids. The early rise of autoimmune disease in CO-fed mice was closely linked to the loss of T-cell function. Both IL-2 production and IL-2 receptor expression were reduced due to the loss of naive T-cells and a rise in memory T-cells. Proliferative response to both mitogens and superantigens (staphylococcal enterotoxins A and B) was higher in FO-fed 6.5-mon-old mice. These changes paralleled decreased PGE2 production by splenic cells from FO-fed mice. Analysis of mRNA expression in different organs revealed differential effects of dietary lipids. In FO-fed mice, transforming growth factor beta 1 (TGF beta 1) expression was decreased in kidneys, but splenic tissues had higher expression of TGF beta mRNA. As TGF beta promotes programmed cell death (PCD), we studied the effects of CO and FO on PCD rates in lymphocytes. Both propidium iodide staining and DNA fragmentation were elevated in lymphocytes of FO-fed mice when compared to CO-fed mice of similar age. Also, increased PCD correlated closely with increased Fas gene expression. Thus, in addition to various other antiinflammatory effects, dietary FO appears to increase PCD and prevent accumulation of self-reactive immune cells in lymphoid organs. Further studies are required to dissect the pro- and antiinflammatory mechanisms associated with dietary n-3 and n-6 lipids in modulating autoimmune disorders or malignancy during aging.
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PMID:Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. 872 1

In the present investigation a study was made on the incidence of antiphospholipid syndrome (APS) on clinical and biological manifestations in a series or 32 patients (28 females and 4 males with a mean age of 25 years) diagnosed of SLE (ARA criteria) and APS (Harris criteria) compared with a group of 25 patients (19 females and 6 males with a mean age of 38 years) diagnosed of SLE without APS. This entails a selection from 124 patients diagnosed of SLE, and an incidence of 25.8% and 9.7% for ACA and LA, respectively. After a clinical protocol was filled, a complete immunological profile was obtained, with lymphocyte subsets, IL-2 receptor, coagulation study, isotype determination for anticardiolipin antibody (ACA), lupus anticoagulant (LA), serology for syphilis and imaging diagnostic techniques. Comparative results, with an statistic assessment, are shown in tables. It is concluded that SLE + APS population can be considered as definite for a peculiar SLE subtype.
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PMID:[The incidence of the antiphospholipid syndrome in the clinical and biological manifestations of systemic lupus erythematosus]. 942 63


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