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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two T-lymphocyte subsets develop in the thymus which differ in the expression of glycoproteins on their cell surface. About 60% of the circulating T cells express the glycoprotein T4, while about 30% have the glycoprotein T8. T4 and T8 cells can be determined in the peripheral blood or various organs with monoclonal antibodies. T4 and T8 cells differ in their antigen recognition, have different functions, and can cause various pathohistological changes. T4 cells recognize the antigen in association with the HLA-D/DR/DP determinants. Upon antigenic stimulation they liberate various factors and initiate and amplify an immune response (T4 = helper/inducer T-cells). They can also be cytotoxic and are mediating effector functions via macrophage activation. T8 cells recognize the antigen in association with HLA-A/B/C determinants. They exert their cytotoxic or suppressive effector functions mainly in viral infections. The T4 or T8 cell-mediated pathohistological changes are discussed in the light of the well studied T-cell infiltrations in lepra lepromatosa or lepra tuberculosa. The T4/T8 cell dyscrasia in the peripheral blood, described in a variety of infectious, autoimmune or immunodeficiency diseases, may be due to enhanced proliferation, selective sequestration, reduced production or the elimination of a subset. T-cell subset analysis in joints, bronchial lavages and tissues has clarified the pathomechanism in a variety of autoimmune diseases, although the etiology remains obscure. For example, in rheumatoid arthritis, multiple sclerosis, and sarcoidosis, a T4 cell-mediated reaction with macrophage activation can be found. T4/T8 cell analysis may also be of value in dissecting heterogenous diseases, e.g. systemic lupus erythematosus. Of value is also the additional demonstration of membrane components reflecting T-cell activation (IL-2 receptor or DR-antigen expression) which serves to identify the activated T-cell subset in peripheral blood. Finally, T4/T8 cell analysis can be helpful in deciding treatment, as the T-cell subsets have a different sensitivity to immunosuppressive drugs.
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PMID:[Analysis of T-cell subpopulations. Pathophysiological concept and significance for clinical medicine]. 315 84

This review covers significant developments in the understanding of the biochemistry and clinical pharmacology of Interleukin-2 (IL-2) that were achieved from 1984 through September 1986. These include developments in the molecular biology of IL-2 and its receptors. Human IL-2 was cloned and sequenced by Taniguchi et al. in 1983. The gene for human IL-2 is located on the long arm of chromosome 4. The secondary structure of the gene is predominantly alpha helix. The mature gene product is a 133 amino acid glycoprotein with a molecular weight of 15,420 Daltons. The IL-2 receptor was revealed to be a glycoprotein of 272 amino acids. The mature receptor has a molecular weight of 55,000 Daltons. A more precise understanding of the mechanism of action IL-2, in particular its role in the induction of the IL-2 receptor, and aspects of the control of IL-2 production was also achieved. Metabolic and morphologic studies have revealed that activation of the T-cell antigen receptor renders the cells responsive to IL-2, but does not move them through the cell cycle. Rather, it appears that IL-2 stimulates G1 progression to S phase ie. blastic transformation. During this progression the cellular proto-oncogene c-myb is induced transiently to 6 to 7 times basal levels. The role of IL-2 as a growth factor for several subsets of T cells has been confirmed, and a new role as a growth factor for B cells was defined. Most importantly, IL-2 was shown to be directly mitogenic for and to expand subpopulations of peripheral blood cells, termed lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). A number of pathologies of IL-2 production or activity have been defined, including Hodgkin's disease, graft versus host disease, systemic lupus erythematosus, lepromatous leprosy, acquired immune deficiency syndrome, and adult T cell leukemia. Murine and human in vivo studies reviewed here have revealed significant parameters of the therapeutic potential as well as the toxicity of this growth factor. Finally, the modulation of IL-2 receptors on human PBL's by thymosin fraction 5 and thymosin alpha 1 suggests that it might be possible to up-regulate IL-2 receptor expression in certain disease states and thus increase the efficacy of IL-2.
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PMID:Recent advances in the understanding of the biochemistry and clinical pharmacology of interleukin-2. 354 63

We studied natural killer cell-mediated (NKCM) activity and its enhancement by interleukin-2 (IL-2) in 15 patients with mixed connective tissue disease (MCTD). The mean baseline NKCM activity of peripheral blood mononuclear cells (MNC) against K562 target cells in the 51Cr release assay was found to be similar to that found in age/sex-matched controls. MCTD patients' cells, however, responded significatively less to IL-2 induction of NKCM than did those of the controls. Using the single-cell agarose NK assay, we found that MCTD patients have a small number of active NK cells that exhibit a high rate of recycling capacity in the baseline state. These preactivated cells could not be stimulated further by IL-2. In two MCTD patients the response to IL-2 was nil, and in the serum from both of them we found an IgM inhibitory factor of such IL-2 induced enhancement. This factor could be absorbed only partially by normal MNC and NK cell-depleted MNC but completely by an IL-2-dependent T-cell line, suggesting that the inhibitory factor may be acting on the IL-2 receptor. These findings seem to be different from those reported in systemic lupus erythematosus and strengthen the notion that MCTD is due to a different immunoregulatory aberration.
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PMID:Natural killer cell-mediated activity in mixed connective tissue disease and its response to induction by interleukin-2. 661 47

A soluble form of CD14 (sCD14) was assessed with an ELISA assay in the serum of the following three clinical groups: 35 patients with an inactive phase of systemic lupus erythematosus (SLE), 17 patients with SLE relapses, and 65 normal healthy volunteers. Increased levels of sCD14 were observed in all patients suffering from SLE compared with normal controls. In addition, patients with active SLE revealed higher serum concentrations of sCD14 (median 6.9 mg/l) than patients under remission (4.1 mg/l; P < 0.0001). Serum values of sCD14 correlated neither with the number of peripheral blood monocytes bearing the CD14 membrane antigen, nor with serum concentrations of IL-1 beta. Serum sCD14 was compared with other clinical parameters used to monitor the clinical course of patients with SLE, among them complement C3, anti-dsDNA antibodies and soluble IL-2 receptor (sIL-2R). A good correlation emerged between sCD14 and C3 as well as sIL-2R concentrations, but sCD14 and anti-dsDNA titres disclosed no significant correlation in both groups of patients with SLE. Serial studies in patients with severe SLE showed that serum sCD14 closely parallels the clinical course as defined by an activity score. Our data suggest that serum sCD14 represents a promising parameter to monitor disease activity in patients with SLE.
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PMID:Elevated levels of soluble CD14 in serum of patients with systemic lupus erythematosus. 751 5

Successful T cell activation via the T cell receptor (TCR)/CD3 complex requires at least one contact-dependent second signal delivered by costimulatory molecules, including the B7/BB1 molecule, that are present on antigen-presenting cells (APC). SLE is characterized by multiple complex lymphocyte abnormalities of undefined molecular origin. It is currently unclear whether an intrinsic defect of T cell or an underlying APC dysfunction is responsible for defective in vitro proliferation of T cells from patients with SLE. We planned the present experiments to ask whether the TCR/CD3-mediated and B7/BB1-costimulated T cell proliferation is normal in these patients. We used enriched T cell populations that were stimulated with an anti-CD3 MoAb in the presence of controlled quantities of functional B7/BB1 antigen. Freshly isolated T cells from 17 SLE patients (10 and seven patients with either active or inactive disease, respectively) and 11 normal individuals were cocultured with irradiated B7/BB1-transfected P815 cells or parental P815 cells in the presence of OKT3 MoAb at optimal and suboptimal concentrations for 2.5-7 days. Normal or SLE T cells responded similarly to stimulation via anti-CD3, in the absence of B7/BB1 antigen. A several-fold increase in T cell proliferation in the presence of B7/BB1 antigen was observed. Proliferation was inhibited in the presence of anti-B7/BB1 MoAb, but not with control MoAbs. Interestingly, dose-response curves and time kinetics of B7/BB1 costimulation were similar in T cells from patients with either active or inactive SLE at the time of study, and normal individuals. In addition, no differences in the IL-2 receptor release by T cells cultured under these conditions were observed between SLE patients and normal individuals. These results demonstrate that CD28 signalling is not intrinsically impaired in patients with SLE; further studies to investigate whether abnormal B7/BB1 expression is involved in the autoimmune process are needed.
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PMID:B7/BB1 provides an important costimulatory signal for CD3-mediated T lymphocyte proliferation in patients with systemic lupus erythematosus (SLE). 751 10

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

Autoimmune MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop a systemic lupus erythematosus-like disease accompanied by a profound lymphadenopathy that consists of CD4-8-B220+ alpha beta T cells. By the use of cross-linking experiments with radiolabeled interleukin-2 (IL-2), these abnormal T cells have been reported to constitutively express the IL-2 receptor beta chain (IL-2R beta), a signal transducing component of IL-2R, in the absence of the alpha chain (IL-2R alpha). To critically reevaluate the role of the IL-2/IL-2R pathway in the pathogenesis of lymphadenopathy we examined expression of the IL-2R alpha and IL-2R beta in MRL/lpr mice by 125I-IL-2 binding analysis and also by flow cytometric analysis using monoclonal antibodies against each component of the receptor. We found that, contrary to the previous report, the CD4-8-B220+ alpha beta T cells in lymph node (LN) of MRL/lpr mice were negative for both IL-2R alpha and IL-2R beta expression. The lpr liver CD4-8-B220+ alpha beta T cells that had been implicated in the genesis of these abnormal LN T cells were also negative for IL-2R beta expression. Therefore, our results indicate that the IL-2/IL-2R system plays little role, if any, in the expansion of abnormal CD4-8-B220+ alpha beta T cells in MRL/lpr mice.
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PMID:The role of the interleukin-2 (IL-2)/IL-2 receptor pathway in MRL/lpr lymphadenopathy: the expanded CD4-8- T cell subset completely lacks functional IL-2 receptors. 768 88

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

In view of recent data demonstrating increased expression of intercellular adhesion molecule-1 (ICAM-1) in the skin of patients with systemic sclerosis (SSc) we studied whether levels of soluble ICAM-1 (s-ICAM-1) shed into the circulation are increased in patients with this disorder. We also compared blood levels of s-ICAM-1 in SSc with those in systemic lupus erythematosus (SLE) and we investigated any possible association of s-ICAM-1 with soluble IL-2 receptor (s-IL 2R) levels, the latter being considered as a marker of lymphocyte activation. Patients with SSc had increased levels of sICAM-1 compared with healthy control subjects (mean +/- SEM, 587 +/- 34 versus 373 +/- 27 ng/ml, P < 0.0001). Patients with diffuse rapidly progressive disease had the highest s-ICAM-1 levels. No association was observed between the extent of skin or internal organ involvement and s-ICAM-1 levels. Patients with digital ulcers had significantly elevated s-ICAM-1, but not s-IL 2R, levels. No correlation was detected between individual s-ICAM-1 and S-IL 2R levels in SSc patients. These novel findings suggest that circulating s-ICAM-1 levels may be a useful marker of endothelial activation in SSc; however, further studies are needed to determine the role of ICAM-1 in the pathogenesis of this disorder.
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PMID:Circulating intercellular adhesion molecule-1 in patients with systemic sclerosis. 809 61


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