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)

A six-year-old boy with homozygous beta-thalassemia in the favorable class 1 risk group received a bone marrow transplant, from his histocompatible sister. He developed grade IV skin and eye graft-versus-host disease (GVHD) following varicella zoster reactivation. Despite the appropriate prophylactic use of cyclosporin A (CsA), methotrexate (MTX), and prompt treatment with high-dose steroids, GVHD progressed resulting in total body epidermal necrolysis. Anti-IL-2 receptor monoclonal antibodies (anti-IL-2R moAb) in combination with steroids were administered to selectively block the activated T cells. After 27 days of daily administration, followed by 17 doses of alternate-day therapy with anti-IL-2R moAb, the severe skin and eye GVHD resolved. The patient, at two years posttransplant, has full engraftment and immune reconstitution without chronic GVHD (cGVHD). In conclusion, we suggest that in the HLA-genoidentical bone marrow transplantation setting, very severe and steroid-resistant GVHD can be controlled through the use of anti-IL-2 receptor antibodies which specifically block the activated IL-2 receptor expressing T cells.
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PMID:Blockade of acute grade IV skin and eye graft-versus-host disease by anti-interleukin-2 receptor monoclonal antibody in genoidentical bone marrow transplantation setting. 967 28

We examined the effect of OK-432 on induction of cytotoxic T lymphocytes (CTL) directed against autologous tumor cells (ATC) and lymphokine-activated killer (LAK) cells from mononuclear cells separated from regional lymph node cells (RLMNCs) of 49 lung cancer patients. We also examined the phenotypic changes of RLMNCs during incubation with or without OK-432. Significant CTL activity and LAK activity against ATC developed from RLMNCs after stimulation with OK-432 or IL-2. Sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432 also developed significant CTL activity and LAK activity from RLMNCs. The CTL activity produced by OK-432 alone was as high as the CTL activity developed by IL-2 alone, OK-432 plus IL-2, or IL-2 plus OK-432. There was no significant difference in the CTL activities achieved by these four treatments. The proportion of CD25+ cells in RLMNCs after incubation with OK-432 was twice that before incubation. Although OK-432 increased IL-2 receptor expression on RLMNCs, it showed no synergistic effect with IL-2 in developing CTL and LAK activity. After incubation with OK-432, the proportion of HLA-DR + cells was also increased significantly. Moreover, the proportions of HLA-ABC+ and HLA-DR+ (class I and class II major histocompatibility complex antigens) cells in ATC were significantly larger than in Daudi cells. OK-432 alone could develop CTL activity against ATC from the RLMNCs of lung cancer patients that was as high as that developed by IL-2 alone or by sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432. The CTL developed from the RLMNCs of lung cancer patients may recognize class I and/or II antigens on the surface of ATC. These results indicated that treatment with OK-432 might be therapeutically useful for lung cancer patients as a CTL inducer rather than a LAK inducer.
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PMID:OK-432 develops CTL and LAK activity in mononuclear cells from regional lymph nodes of lung cancer patients. 977 99

One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers.
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PMID:The prognostic significance in HIV infection of immune activation represented by cell surface antigen and plasma activation marker changes. 1008 Aug 36

Immunogold staining and electron microscopy show that IL-2 receptor alpha-subunits exhibit nonrandom surface distribution on human T lymphoma cells. Analysis of interparticle distances reveals that this clustering on the scale of a few hundred nanometers is independent of the presence of IL-2 and of the expression of the IL-2R beta-subunit. Clustering of IL-2Ralpha is confirmed by confocal microscopy, yielding the same average cluster size, approximately 600-800 nm, as electron microscopy. HLA class I and II and CD48 molecules also form clusters of the same size. Disruption of cholesterol-rich lipid rafts with filipin or depletion of membrane cholesterol with methyl-beta-cyclodextrin results in the blurring of cluster boundaries and an apparent dispersion of clusters for all four proteins. Interestingly, the transferrin receptor, which is thought to be located outside lipid rafts, exhibits clusters that are only 300 nm in size and are less affected by modifying the membrane cholesterol content. Furthermore, transferrin receptor clusters hardly colocalize with IL-2Ralpha, HLA, and CD48 molecules (crosscorrelation coefficient is 0.05), whereas IL-2Ralpha colocalizes with both HLA and CD48 (crosscorrelation coefficient is between 0.37 and 0.46). This coclustering is confirmed by electron microscopy. The submicron clusters of IL-2Ralpha chains and their coclustering with HLA and CD48, presumably associated with lipid rafts, could underlie the efficiency of signaling in lymphoid cells.
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PMID:Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts. 1082 48

When interleukin-2 (IL-2) binds to the IL-2 receptor (IL2-R) on activated T cells, a soluble portion of the receptor (sIL2-R) is released. After allogeneic bone marrow transplantation (BMT), the serum concentration of sIL2-R may, therefore, be a useful surrogate marker for T cell activation that results in acute graft-versus-host disease (aGVHD). To determine if the sIL2-R concentration is a useful marker to help establish a diagnosis of aGVHD, serial sIL2-R concentrations were measured weekly for 4 weeks in 43 patients after allogeneic BMT. Grafts were from HLA-matched siblings (n = 33), 5/6 HLA-matched siblings (n = 3) or matched unrelated donors (n = 7). GVHD prophylaxis included cyclosporine A (CSA)/methotrexate (MTX) (n = 25), solumedrol/CSA (n = 15), or T cell depletion (n = 3). Twenty-three patients developed aGVHD (Grade I, 7; Grade II, 12; Grade III, 4) a median of 28 days after transplant. There was a significant association between a clinical diagnosis of aGVHD and an increase in the sIL2-R concentration (p < 0.001). The mean percent increase (+/-SE) over baseline for patients with a clinical diagnosis of aGVHD was 294% (+/-57%) by week 2 (n = 12), 431% (+/-116%) by week 3 (n = 14), and 650% (+/-315%) by week 4 (n = 9) after BMT. For each 100% increase over baseline, the likelihood of having aGVHD increased by 18%. Six of 20 patients without aGVHD became critically ill and exhibited marked increases in sIL2-R concentrations, similar to patients with a clinical diagnosis of aGVHD who never became critically ill. Fourteen patients without aGVHD who did not become critically ill exhibited negligible increases of sIL2-R in 2- to 4-week period after BMT. These data suggest that serial measurements sIL2-R concentration are helpful in establishing the diagnosis of aGVHD, but are not useful in the most acutely ill patients.
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PMID:Soluble interleukin-2 receptor concentration as a biochemical indicator for acute graft-versus-host disease after allogeneic bone marrow transplantation. 1089 61

A newly developed device to simulate microgravity for space biological investigations under laboratory conditions allowed us to apply a reproducible environmental stress on immunologically active cells. Cell proliferation, soluble IL-2 receptor in the culture supernatant, lymphocyte surface activation markers like CD25 (IL-2R), CD69 and HLA-Dr were the endpoints measured. Untreated donor lymphocyte reactions under microgravity were compared to the same cells treated with an immunomodulator from herbal plasmolysed yeast (Bio-Strath Food Supplement). The main finding is the enhancement of the proliferation inhibition under microgravitational stress by the herbal plasmolysed yeast.
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PMID:Mode of action of plasmolysed yeast on lymphocytes under microgravity stress. 1113 Jul 78

The evaluation of the changes of lymphocytes: T(CD3), B (CD19), subpopulations CD4, CD8, active lymphocytes CD3 + HLA-DR+, lymphocytes with the receptor for IL2(CD3 + CD25+), NK cells as well as the CD4/CD8 ratio in 30 patients with the early localized (group I n = 7) and early disseminated (group II n = 23) type of Lyme disease, before (examination 1) and after the antibiotic therapy (examination 2) was performed. Group III was composed of 90 healthy people. Measurements were carried out in an COULTER EPIC XL cytoflowmeter, using Becton Dickinson antibodies. Statistical analysis was performed using AnStat software. In the examined groups, a decrease of the subpopulations of CD4, CD8 lymphocytes in comparison with healthy subjects was revealed, as well as a decrease of the CD4/CD8 ratio after treatment. A considerably lower percentage value of active lymphocytes CD3 + HLA-DR+ in both groups and the reduction of the NK subpopulation before and after treatment of early disseminated Lyme disease in comparison with healthy people was observed. The higher percentage values of the lymphocytes with IL-2 receptor were not statistically significant. The indicated essential changes in the subpopulations of T lymphocytes, characterized by a decrease before the antibiotic therapy and by the tendency towards an increase after that therapy of the percentage of CD4, CD8, NK and CD3 + HLA-DR+ lymphocytes in peripheral blood, point out their role in the immunopathogenesis of the Lyme disease. The absence of the complete normalization of the examined parameters after the treatment, on the one hand, may provide evidence for some inertia of the elements of the immune system, on the other hand can also result from too short antibiotic therapy and maintenance of the antigenic stimulation.
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PMID:Subpopulations of the peripheral lymphocytes in the early clinical forms of Lyme disease. 1120 23

Sixty eight patients with verified multiple sclerosis (MS) (mean EDSS score 3.1 +/- 1.0) and 50 healthy donors have been investigated. Thirty five patients had relapsing-remitting, 25--secondary progressive, 8--primary progressive course. The remission was in 38, decompensation--in 20, relapse--in 10 patients. Lymphocyte subpopulations were investigated using monoclonal antibodies (Moscow) to the following antigens: CD3 (T-lymphocytes), CD4 (T-helpers), CD8 (T-supressors), CD20 (8-lymphocytes), CD25 (IL-2 receptor), CD16 (natural killers), CD95 (activated cells ready to apoptosis). Cytokines and tumor necrosis factor-alpha (TNF-alpha) levels were measured using ELISA test. HLA antigens were investigated by standard lymphocytotoxic test. In MS we found a fall of CD3, CD4, CD8, CD20 and CD16, but an increase of CD4/CD8, CD95, CD25. The CD95 level correlated with CD4, CD4/CD8 and CD16. In MS spontaneous IL-2, IL-6, IL-8 and TNF-alpha production was raised and stimulated IL-6 and IL-8 secretion was reduced. IL-4, IL-6, IL-8, TNF-alpha and IL-1 beta serum production in vivo was elevated. We found an increase of CD3, CD4, CD16, CD25, but a decrease of IL-1 (p < 0.01) spontaneous production and IL-6, IL-8, TNF-a stimulated secretion in DR2(+) MS patients, comparing to DR2(-) patients and controls. In DR2(-) patients as compared to DR2(+) patients and controls, all lymphocyte subpopulations levels, especially CD8 (p < 0.001) one, were decreased, but spontaneous IL-8 (p < 0.01) production was increased. The data obtained indicate lymphocyte apoptosis activation, targeting promoted lymphocyte destruction, and suggest T helper type-1 reaction prevalence in MS.
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PMID:[Immunogenetic cytokine restriction in multiple sclerosis]. 1158 2

In this clinical study, we have examined 10 patients with ulcerative colitis. The study group included 5 men and 5 women. The control group consisted of 6 patients with negative colonoscopic finding performed for differential diagnosis of the dyspeptic syndrome. Patients with ulcerative colitis were divided into two groups according to the clinical pattern, macroscopic endoscopic finding, and histological examination of the bioptic specimens. The Ist group of patients with active stage of ulcerative colitis, the IInd group of patients in remission, without clinical and endoscopic signs of disease activity. We have found that from the followed markers the greatest importance lies in the determination of the standard immunologic profile of the mucosa, the determination of activating markers HLA-DR+, CD69, CD122 and CD71 on T-lymphocytes and CD69 and CD71 on B-lymphocytes. The differences between the control group and the group of patients in active stage of the disease were statistically significant. Statistical significance was also found in some of the above-mentioned parameters when comparing the group of active disease and that one in remission (CD4/CD8 ratio, HLA-DR+, CD122 on T-lymphocytes). Our results imply that the changes in the target tissue contribute to more precise assessment and follow-up of therapeutic effect in non-specific inflammatory bowel disease.
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PMID:[Importance of determination of lymphocytes in intestinal mucosa biopsy specimens using flow cytometry in the evaluation of ulcerative colitis activity]. 1196 80

A 36-year-old woman was referred to our hospital because of leukocytosis in June 2000, and was admitted to our hospital and diagnosed as having adult T-cell leukemia/lymphoma (ATL; acute type). Complete remission was achieved with eight courses of CHOP therapy, but ATL relapsed and she was readmitted to our hospital in September 2001. Laboratory examination showed elevated levels of serum LDH and soluble IL-2 receptor, and hypercalcemia. CT examinations showed swelling of the abdominal lymph nodes and hepatosplenomegaly. CHOP therapy improved the symptoms, but recrudescence soon occurred. After two courses of salvage therapy which resulted in no remission, the patient received an allogeneic peripheral blood stem cell transplant (allo-PBSCT) from her HLA-matched sibling donor after preconditioning with BU + CY in January 31, 2002. Cyclosporin A (CsA) and short-term MTX were used to prevent GVHD. Bone marrow engraftment was prompt and acute GVHD was not found. Two months later, recurrence was seen in the form of subcutaneous tumors, but the tumors spontaneously disappeared following CsA withdrawal. At the time of writing, eight months after the transplant, remission has been maintained. A graft-versus-leukemia (GVL) effect may have been the curative action in this case.
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PMID:[Cyclosporin A withdrawal causes spontaneous remission of recurrent subcutaneous tumors after allogeneic peripheral blood stem cell transplantation for adult T-cell leukemia/lymphoma]. 1269 82


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