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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 BB rat is a model of spontaneous autoimmune diabetes. To characterize quantitatively all known immune cell subsets involved in disease pathogenesis, FACS analysis of spleen cells was performed in diabetes-prone (DP) and acutely diabetic (D) BB rats and compared with diabetes-resistant (DR) BB and normal Wistar-Furth (WF) strains. We observed increased percentages of splenic NK cells in DP and D animals compared with DR rats using an NK-specific monoclonal antibody. We found increased proportions of splenic macrophages in the T-lymphopenic DP and D rats and low macrophage contents in DR spleens compared with WF spleens. We observed that percentages of the CD4-CD8- T cell receptor alpha/beta+ (double-negative) T cell subset were strikingly increased in the lymphopenic DP and D animals, compared with DR animals. We observed increased percentages of activated splenic CD5+ T cells expressing the IL-2 receptor and MHC class II antigen in DP and D rats compared with DR animals. Our studies suggest that (a) splenic NK cells and macrophages quantitatively appear to be involved in the pathogenesis of diabetes; (b) double-negative T cells escape from the T cell depletion process; (c) a marked increase of activated splenic T cells suggests diabetes is associated with general T cell activation processes; and (d) an altered balance among the different immune cell subsets may in part explain the pathogenesis of diabetes, since marked relative changes are observed when comparing the DR strain to the DP strain in both the prediabetic and diabetic stages.
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PMID:Quantitative analyses comparing all major spleen cell phenotypes in BB and normal rats: autoimmune imbalance and double negative T cells associated with resistant, prone and diabetic animals. 138 37

IL-2 receptor positive T-cells from leukocyte-infiltrated pancreatic islets of diabetes prone or acutely diabetic NOD mice were propagated in vitro by culture in interleukin-2 containing medium. Of 13 lines obtained after limiting dilution all were positive for the T-cell marker Thy-1 and for CD8. Considerable heterogeneity in T-cell receptor usage was noted. Seven lines expressed T-cell receptors using V beta 8, one line was positive for V beta 5 and two lines expressed a non V beta 5, non V beta 8 receptor. Finally, two further lines lacked T-cell receptors. None of the cell lines were cytotoxic to islet cells although 10 lines showed non MHC restricted lysis of one or more tumour cells including rat insulinoma cells. We conclude that IL-2 receptor positive CD8+ T-lymphocytes from NOD islets are heterogenous with respect to V beta T-cell receptor usage. The majority of these cells are not cytotoxic to islet cells.
Diabetes Res 1991 Feb
PMID:Analysis of IL-2 receptor positive CD8(+)-T-lymphocytes grown from islets of NOD mice. 168 10

A 66-year-old female suffering from HTLV-1 associated myelopathy (HAM) for more than 30 years was hospitalized because of memorial impairment, deafness, dysarthria, dysphagia, and complete paraplegia. She first noticed stiffness and weakness of the right leg at 35 years of age. Gait disturbance was slowly progressed and complete paraplegia developed 18 years later. Neurological examinations on admission revealed that she was bedridden with decubitus, mental deterioration (pre-dementia of subcortical type), bilateral optic nerve atrophy, severe sensory-neural deafness, dysarthria, complete paraplegia, and marked neurogenic bladder. Laboratory data showed mild normocytic anemia and moderate diabetes mellitus. Anti-HTLV-1 antibody titers in serum and CSF were 78,192X and 1,024X, respectively (PA method). Serum levels of soluble IL-2 receptor was markedly elevated (2,200 U/ml). Peripheral blood lymphocytes showed spontaneous proliferation when cultured for 5 days (3H-thymidine uptake; 45,285 cpm/5 X 10(4) cells). MRI examinations of the spinal cord disclosed a predominant atrophy of lower thoracic cord without any compressive lesions. Brain MRI showed diffuse high intensity lesions of the periventricular area on T2 weighted images. Such abnormalities were predominantly found in fronto-parietal region and were quite similar to those of leuko-ariosis. Single photon emission CT using 123I-iodoamphetamine showed hypoperfusion of cerebral white matter on delayed image. It has been reported that intellectual impairment and brain atrophy are not usually seen in HAM patients. The present case, however, shows that such abnormalities of the central nervous system could occur in HAM patients with a long duration of illness.
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PMID:[A case of HTLV-1 associated myelopathy progressed in course over 30 years]. 189 70

The fact that insulitis occurs also in normoglycaemic BB rats led us to investigate the phenotypes of lymphocytes invading the pancreatic islets of prediabetic BB/OK rats in comparison to age- and sex-matched normoglycaemic animals in a retrospective analysis. By using a panel of monoclonal antibodies we investigated the number of pan T-cells, T-helper cells, cytotoxic T-cells and NK-cells and determined the number of activated cells by measurement of class I, class II and IL-2 receptor positive cells. The bound primary antibodies were visualized using the APAAP-technique. The prediabetic rats showed a significantly decreased pancreatic insulin content which was drastically reduced at diagnosis of diabetes. This was accompanied by reduction of the B-cell volume density. The prediabetic as well as the long-term normoglycaemic BB rats showed an accumulation of mononuclear cells (all phenotypes investigated) within the pancreatic islets. Concerning the phenotypes of infiltrating cells there was no qualitative difference between long-term normoglycaemic and prediabetic rats but quantitatively an enhanced amount of W3/25+, OX-8+, OX-6+ and ART-18+ cells could be observed in the prediabetic animals. From our results we conclude that an immunological B-cell destructive process occurs also in long-term normoglycaemic BB rats by participation of mononuclear cells qualitatively not different from those observed in prediabetic animals. Activated T-cells (OX-19+, OX-8+, W3/25+) expressing class II antigens (OX-6+) and the IL-2 receptor (ART-18+) seem to play a significant role in the amplified immunological pancreatic B-cell destruction.
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PMID:Different lymphocyte subset distribution within "insulitis" islets of normoglycaemic and prediabetic BB/OK rats of similar age. 218 40

Seventy patients aged 15-40 yr with recent-onset insulin-dependent diabetes mellitus (IDDM) were entered into a double-blind trial, in which they were randomly assigned to either cyclosporin (7.5 mg.kg-1.day-1) or to placebo and were monitored for 1 yr for various phenotypic and functional parameters of T-lymphocyte-mediated immunity. Before treatment, the proportions of total T-lymphocytes (CD3+) and helper-inducer T-lymphocytes (CD4+) were normal, whereas significantly decreased values of suppressor/cytotoxic T-lymphocytes (CD8+), as compared with normal controls, were found in 31% of the patients. The interleukin 2 (IL-2)-receptor expression was significantly increased in IDDM patients compared with control subjects, although the single values were low: patients, 2.02 +/- 0.41%; controls, 0.88 +/- 0.25% (means +/- SE). Circulating levels of soluble IL-2 receptor were also significantly increased in IDDM patients compared with controls: patients, 372.3 +/- 25.4 U/ml; controls, 235.5 +/- 29.3 U/ml (means +/- SE). However, no major abnormalities were found in mitogen (phytohemagglutinin)-induced IL-2 production, cell proliferation, or IL-2-receptor expression. After 6 mo of cyclosporin treatment, no major modifications of any of the parameters analyzed were noted, even in patients who had cyclosporin blood trough levels greater than 300 ng/ml, i.e., the threshold value associated with clinical efficacy. One explanation for the absence of a major effect of cyclosporin, in contrast with its demonstrated clinical effectiveness, is the reversibility of its activity. Our results preclude the use of the described tests to reliably monitor IDDM patients undergoing immunosuppressive therapy.
Diabetes 1989 Feb
PMID:Effect of cyclosporin on interleukin 2-related T-lymphocyte parameters in IDDM patients. 264 44

We studied interleukin 1 (IL-1) and interleukin 2 (IL-2) production in unstimulated and stimulated cultures from 27 young diabetic patients and 21 age-matched healthy subjects. In unstimulated cultures monocytes from newly diagnosed patients produced significantly higher levels of IL-1 than controls. In lipopolysaccharide (LPS)-stimulated cultures, IL-1 production in patients with fresh and long-standing diabetes was no different from that of controls. IL-2 production was low or absent in unstimulated cultures from insulin-dependent diabetes mellitus (IDDM) patients and controls. In phytohaemagglutinin (PHA)-stimulated cultures both patient groups produced significantly less IL-2 than controls. No correlation was observed between IL-1, IL-2 production and HbA1 levels or the presence of HLA-DR3 or DR4. Our data on "spontaneous" IL-1 production support the hypothesis that monocytes from some newly diagnosed IDDM patients may circulate in a "preactivated" state. The low levels of IL-2 might be explained by an abnormal consumption or by the presence of increased soluble IL-2 receptor levels or by a serum factor which interferes with IL-2 production. Alternatively, it may be a genetically determined trait.
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PMID:Alterations of in vitro interleukin 1 and 2 in diabetic children. 279 22

Alterations in T-lymphocyte subsets have been connected to the autoimmune pathogenesis of Type 1 (insulin-dependent) diabetes. In this study peripheral blood lymphocytes were analysed by flow cytometry using OKT3, OKT4, OKT8, anti-HLA-DR, anti-IL-2 receptor and anti-membrane immunoglobulin antibodies in newly diagnosed Type 1 diabetic children, their healthy siblings and healthy control children. The results were compared to the occurrence of serologically verified recent virus infections, some of which can induce lymphocyte subset alterations and have also been connected with the onset of diabetes. In most diabetic patients the amounts of OKT3, OKT4, OKT8 and membrane-Ig-positive cells were within the normal range. Exceptional helper/inducer and suppressor/cytotoxic T cell profiles were observed in a few patients, most of whom had serologically verified recent Epstein-Barr, rubella, mumps or Coxsackie B virus infection. In addition, increased numbers of activated IL-2 receptor-positive cells were observed in the patient group. These results suggest that significant lymphocyte subset alterations are not characteristic of Type 1 diabetes but can occasionally be induced by recent virus infections in newly diagnosed patients. However, the slight increase in activated lymphocytes could reflect the activation of cellular immune systems to the autoantigens in the pancreas.
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PMID:Flow-cytometric analysis of lymphocyte subsets in relation to virus infections at the onset of type 1 (insulin-dependent) diabetes. 284 9

Twenty-five recently diagnosed insulin-dependent diabetic patients were screened for the presence of activated T lymphocytes using the anti-IL-2 receptor monoclonal antibody; thirteen had elevated levels of activated T lymphocytes. The activated cells were mostly confined to the CD4 subset, with the CD4/CD8 ratio in IL-2 receptor expressing cells averaging 5 +/- 1 (s.d.) compared with 1.3 +/- 0.3 for all T cells. In recent onset insulin-dependent diabetes blood there was no lack of CD4 CD45R+ (suppressor/inducer) T cells. The activated IL-2 receptor, expressing cells belonged to both CD4 subsets, 'helper inducer' (CD44B4) and 'suppressor inducer', (CD42H4).
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PMID:The majority of the activated T cells in the blood of insulin-dependent diabetes mellitus (IDDM) patients are CD4+. 297 27

The expression of activation antigens (transferrin receptor, IL-2 receptor and Ia antigen) on circulating T lymphocytes from Japanese children with Type 1 diabetes was studied using five monoclonal antibodies (Ab), OKT9, anti-Tac Ab, OKIa1, anti-human HLA-DR Ab and OKT3. For detecting Ia positive T cells, the dual staining technique using OKT3 and anti-Ia antibody was employed. Four out of six patients (67%) with newly diagnosed Type 1 diabetes showed a raised level of either OKT9 or Tac positive cells when examined at diagnosis. These patients, however, rapidly lost these activation antigens after the insulin therapy was started. In contrast, in 32 long-standing patients, only 2 (6%) had a high percentage of OKT9 positive cells and none of them demonstrated Tac positive cells. One out of six newly diagnosed patients or three out of 21 long-standing patients had a significantly high percentage of Ia-positive T cells compared with normal subjects. In poorly controlled long-standing patients whose HbA1 value was higher than 14%, none of them had an increased number of activated lymphocytes. Therefore, it is unlikely that insulin deficiency and hyperglycemia were responsible for the changes observed in these studies. Activated lymphocytes might be related to activation of the immune system involved in pathogenesis of Type 1 diabetes.
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PMID:Activated lymphocytes in patients with newly diagnosed type 1 (insulin-dependent) diabetes mellitus. 309 6

Recently, the presence of a soluble form of IL-2 receptor (IL-2RS) in human sera and in supernatants of PHA-stimulated lymphocytes has been demonstrated. It has been suggested that autoimmune diseases could be characterized by a defect in production of IL-2RS, unlike immunoproliferative disorders which are characterized by overproduction. Our aim was to investigate serum IL-2RS levels in 35 newly diagnosed Type 1 diabetic patients, in 25 age-matched healthy blood donors and in five patients with Hodgkin's disease. We found that newly diagnosed diabetic patients have higher IL-2RS levels (424.8 +/- 203 U/ml) than normal controls (252.4 +/- 38.4 U/ml) (p less than 0.005). In 22 out of 35 patients (62.8%) the IL-2RS values were above the higher 95% tolerance limit of controls. Furthermore, the persistence of high IL-2RS levels was observed in 18/35 diabetic patients six months after diagnosis (470 +/- 195.6 U/ml). The increased levels were not correlated with glycaemic and HbA1c levels and patients' age. Our findings suggest a potentially significant role for the released IL-2R in the regulation of IL-2 dependent lymphocyte functions in Type 1 diabetes. The study of IL-2RS in Type 1 diabetes may provide a new tool for the knowledge of cytokine involvement in the disease.
Diabetes Res 1988 Jul
PMID:Increased soluble interleukin-2 receptor levels in the sera of type 1 diabetic patients. 326 1


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