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 influence of a 1-hour neuropsychological stress test on the distribution of lymphocyte subpopulations and on plasma catecholamine levels was investigated in 18 patients with rheumatoid arthritis (RA) and 14 sex- and age-matched controls. Despite significant increases in lymphocyte counts in both groups, lymphocyte subsets did not change accordingly. A wide scattering of catecholamine levels in plasma before and after stress was observed. Plasma levels of lymphokines such as interleukin (IL)-1 beta and IL-6 could not be detected in RA patients. Enzyme immunoassay of markers of lymphocyte activation such as HLA-DR and cell-bound IL-2 receptor showed only a significant elevation of HLA-DR marked cells in RA patients at baseline. Significantly higher amounts of the soluble IL-2 receptor were detected in patients with RA before the stress test, but stress testing did not alter this parameter. In conclusion, lymphocyte activation in RA and a defect in the expression of IL-2 receptor on the cell surface of lymphocytes were confirmed in the present study.
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PMID:Modulation of lymphocyte subsets due to psychological stress in patients with rheumatoid arthritis. 145 83

An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.
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PMID:Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness. 156 2

Interstitial pneumonia is well known as one of the complications of rheumatoid arthritis (RA). While interleukin-2 (IL-2) regulates the immune response through IL-2 receptor (IL-2R), the exact role of the soluble form of IL-2R (sIL-2R), recognized as a part of the alpha chain or IL-2R, is still obscure. So, the immunological significance of sIL-2R in serum and in bronchoalveolar lavage fluid (BALF) of those of RA patients with or without interstitial pneumonia was studied. The sIL-2R was measured with an ELISA kit (T-Cell Science Ltd). The levels of sIL-2R in the sera of RA patients without interstitial pneumonia were significantly higher than those of normal controls. Furthermore, the levels of sIL-2R showed a statistically significant correlation with ESR and Lansbary's index. The levels of sIL-2R of RA patients with interstitial pneumonia were higher than in those without interstitial pneumonia although the evaluation of class and stage of arthritis in those RA patients with or without interstitial pneumonia revealed no significant difference. A high sIL-2R/albumin ratio in BALF of RA patients with interstitial pneumonia was shown in comparison with those of normal control. These data indicate that the estimation of sIL-2R in RA patients could be useful in estimating the disease activity and that high levels of sIL-2R reflect the active immune response in the lungs of RA patients with interstitial pneumonia.
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PMID:[The significance of soluble IL-2 receptors in rheumatoid arthritis with interstitial pneumonia]. 157 40

DAB486IL-2 is an interleukin-2 receptor-specific cytotoxin which selectively targets and kills cells which bear the high-affinity form of the IL-2 receptor. Since elimination of activated T lymphocytes may be useful in the treatment of rheumatoid arthritis, the effect of DAB486IL-2 treatment in an animal model of arthritis was investigated. We demonstrated that rats treated with DAB486IL-2 during the induction phase of disease have delayed onset of symptoms and significantly reduced severity of inflammation as well as a depressed proliferative response to mycobacterial stimulation in vitro. In addition, the presence of preexisting antibodies to the molecule had no impact on the anti-arthritic effects observed in this model. These data suggest that DAB486IL-2 may have therapeutic potential in the treatment of rheumatoid arthritis.
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PMID:Anti-arthritic effects demonstrated by an interleukin-2 receptor-targeted cytotoxin (DAB486IL-2) in rat adjuvant arthritis. 162 18

Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase, in nanomolar concentrations blocks proliferative responses of cultured human, mouse and rat T lymphocytes and B lymphocytes to mitogens or in mixed lymphocyte reactions. The inhibitory effect of MPA on lymphocyte proliferation is reversed by addition to culture media of deoxyguanosine or guanosine but not by addition of deoxyadenosine or adenosine. The findings suggest that the principal mechanism of action of low concentrations of MPA is depletion of deoxyguanosine triphosphate which is required for DNA synthesis. In immunosuppressive doses, MPA does not affect the formation of IL-1 by LPS-activated human peripheral blood monocytes. Unlike cyclosporin A and FK-506, MPA does not inhibit the formation of IL-2 and the expression of the IL-2 receptor in mitogen-activated human T lymphocytes. MPA suppresses mixed lymphocyte reactions when added 3 days after their initiation. These findings suggest that MPA does not inhibit early responses of T and B lymphocytes to mitogenic or antigenic stimulation but blocks the cells at the time of DNA synthesis. The cytostatic effect of MPA is more potent on lymphocytes than on other cell types, such as fibroblasts and endothelial cells. MPA also inhibits antibody formation by polyclonally activated human B lymphocytes. MPA is an immunosuppressive agent reversibly inhibiting proliferation of T and B lymphocytes and antibody formation, with a profile of activity different from that of other immunosuppressive drugs. Human T and B lymphocytic and promonocytic cell lines are highly sensitive to the antiproliferative effects of MPA, whereas the erythroid precursor cell line K562 is less susceptible. The effect of MPA on cells of the monocyte-macrophage lineage could exert long-acting anti-inflammatory activity. MPA or analogues may have therapeutic utility in diseases such as rheumatoid arthritis, for prevention of allograft rejection and in lymphocytic or monocytic leukaemias and lymphomas.
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PMID:Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion. 182 93

Tripterygium wilfordii Hook F (TWH) is a vine-like plant that grows in a wide area of south China. An alcohol extract of this plant known as T2 has been suggested to be effective in the treatment of rheumatoid arthritis (RA). To examine the mechanism by which this herbal remedy might be effective in RA, the capacity of T2 to alter human immune responsiveness in vitro was investigated. Human peripheral blood mononuclear cells were obtained from normal adults and separated into purified populations of monocytes, T cells, and B cells. T2 at 0.1-1 micrograms/ml inhibited antigen- and mitogen-stimulated proliferation of T cells and B cells, interleukin-2 (IL-2) production by T cells, and immunoglobulin production by B cells. T2 did not affect IL-2 receptor expression by T cells, IL-1 production by monocytes, or the capacity of monocytes to present antigen. Inhibition could not be accounted for by nonspecific toxicity. These results support the conclusion that T2 exerts a powerful suppressive effect on human immune responses. This action might account for its therapeutic effectiveness in RA.
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PMID:Effect of an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F on human immune responsiveness. 193 Mar 17

Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis.
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PMID:Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen. 221 3

We studied the levels of membrane-bound and soluble-form interleukin 2 (IL-2) receptors in forty patients with rheumatoid arthritis. Levels of IL-2 receptors in the sera and synovial fluid of patients with rheumatoid arthritis were elevated when compared to values observed in normal sera and synovial fluid derived from the osteoarthritic joint. Simultaneous elevation of IL-2 receptor expression in blood and synovial fluid lymphoid cells was also detected, but no correlation was found between the two parameters nor between serum IL-2 receptor levels and the hemosedimentation rate. We conclude that measurement of serum concentrations of soluble IL-2 receptors should be used with caution as an index of disease activity, but may be useful when used in conjunction with other parameters in the management of patients with rheumatoid arthritis.
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PMID:Simultaneous evaluation of membrane bound and soluble interleukin 2 receptor expression in the blood and synovial fluid of patients with rheumatoid arthritis. 228 27

Monoclonal antibodies to certain cell surface constituents on lymphocytes, monocytes and macrophages have been administered to Lewis rats with developing, established or adoptively transferred arthritis, to determine any immunomodulatory properties. Anti-CD4 antibodies against helper T-lymphocytes produced a dose related inhibition of developing arthritis; high dose levels completely suppressed all symptoms of arthritis and these rats were resistant to further attempts to induce arthritis. Anti-Ia (MHCII) antibodies also inhibited arthritis in a dose related manner; anti-pan T antibodies delayed the onset of arthritis, but antibodies against CD8 and IL-2 receptor positive cells were without effect. Development of type II collagen-induced arthritis was also inhibited by anti-CD4 treatment. Established arthritis could be temporarily inhibited by anti-CD4 antibodies, but rebound of arthritis invariably occurred after stopping treatment, as is the case with cyclosporin A. Similar results with anti-CD4 antibodies were obtained during treatment of arthritis adoptively transferred by arthritogenic T-lymphocytes. From these experiments it is clear that CD4 positive T-lymphocytes have a major role in the induction of adjuvant arthritis and that interaction between CD4 and Ia bearing cells is important. The rebound of arthritis that occurred after withdrawal of anti-CD4 treatment during established disease infers that cells in addition to helper T-lymphocytes are involved in the chronicity of arthritis, but these remain to be elucidated. These findings are discussed in relation to results with monoclonal antibodies in other models of arthritis and human rheumatoid arthritis; the prospects for human therapy are also discussed.
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PMID:Monoclonal antibodies and arthritis. 232 19

Treatment of rheumatoid arthritis (RA) with cyclosporin A (CsA) has been successful, but the adverse effects of the drug have limited its use. We investigated the capacity of another immunosuppressive agent, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], to augment the effects of CsA on in vitro T cell functions. Exposure of CD4+ cells from RA patients or from normal subjects to either molecule alone resulted in a dose-dependent inhibition of phytohemagglutinin stimulation and interleukin-2 (IL-2) production that was more pronounced in cells from RA patients than in cells from normal subjects. Moreover, the action of CsA and 1,25(OH)2D3 on RA patient T cell functions in vitro was synergistic. Thus, in the presence of the vitamin D3 metabolite, only one-hundredth the concentration of CsA was required to produce the same effect on IL-2 production as that produced by CsA alone. IL-2 receptor expression was also reduced by the addition of both drugs. In contrast, IL-1 production by RA monocytes was not affected by CsA and 1,25(OH)2D3, either together or alone, and addition of IL-1 did not restore the ability of CD4+ cells from RA patients to secrete IL-2. Exogenous IL-2 reversed a large part of the inhibitory effect induced by both CsA and 1,25(OH)2D3, indicating that the immunosuppressive properties of these agents are mediated by the inhibition of IL-2 secretion. This synergy between 2 molecules that are biochemically very different suggests the existence of one or several sites of interaction that take place during the early stages of T cell activation.
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PMID:1,25-dihydroxyvitamin D3 potentiates the in vitro inhibitory effects of cyclosporin A on T cells from rheumatoid arthritis patients. 252 53


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