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)

Hemophagocytic lymphohistiocytosis, terminology that designates a syndrome that may be familial or sporadic, with or without an associated viral infection, is presented as the prototype of a hemophagocytic syndrome, a condition in which there is uncontrolled activation of the cellular immune system. Diagnostic criteria include idiopathic fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and the presence of hemophagocytosis. The surgical and autopsy pathology features infiltrates composed of lymphocytes and ordinary, but activated, histiocytes and hemophagocytosis. The chronic hepatitis-like hepatic lesion is noted to be characteristic, if not unique, in this age group and setting. Current concepts of pathophysiology focus on the role of cytokines, particularly interleukin (IL)-1, IL-2, soluble IL-2 receptor, plasminogen activator, and prostaglandins. The clinicopathologic features of the syndrome can be accounted for by the uncontrolled and unopposed production and release of these mediators. Nosology places hemophagocytic lymphohistiocytosis in the position of the most important of the "benign" histiocytosis syndromes that involve ordinary histiocytes of the mononuclear phagocytic system in contrast to Langerhans cell histiocytosis (histiocytosis X) in which pathological dendritic histiocytes are operative. Features that distinguish hemophagocytic lymphohistiocytosis from other disorders, such as malignant histiocytosis, X-linked lymphoproliferative disorder, congenital immunodeficiency states, the accelerated phase of Chediak-Higashi syndrome, and cytophagic histiocytic panniculitis, which may be associated with a hemophagocytic syndrome, are presented.
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PMID:Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. 156 89

Three lines of transgenic mice carrying the human T-cell lymphotropic virus type 1 tax gene have previously been reported to develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1329, 1987). Tumors from these mice and tumor cell lines derived from them expressed high levels of tax RNA and protein. They also expressed high levels of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene as measured by proliferative responses of FD-CP1 target cells using conditioned media from tumor cells and by Northern (RNA) blot analysis of RNA from tumors and tumor cell lines. Although other tissues, such as salivary glands and muscles, in the transgenic mice also expressed high levels of tax, they did not express the gene for GM-CSF. This indicates that tissue-specific cellular factors, in addition to tax, are required for GM-CSF gene expression. Systemic effects of excessive GM-CSF production were demonstrated by infiltration of polymorphonuclear leukocytes into tumor tissues which are not necrotic, by peripheral granulocytosis, and by splenomegaly resulting from myeloid hyperplasia. The interleukin-2 (IL-2) receptor was also found to be expressed by the tumors and tumor cell lines as measured by IL-2-binding and cross-linking studies. This is the first demonstration that the IL-2 receptor can be activated by tax in a nonlymphoid cell type. These in vivo findings are consistent with other reports which have demonstrated in vitro cis-regulatory elements within the 5'-flanking regions of the genes for GM-CSF and the IL-2 receptor which are responsive to trans activation by the tax gene.
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PMID:trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene. 268 63

Glycyrrhizin (GL), a plant extract, has been evaluated for its inhibitory effect on HIV replication in vitro and for its improvement of clinical symptoms in HIV-infected patients. In this study, we used GL in a murine AIDS model (MAIDS) to evaluate these effects. C57BL/6 mice were inoculated with LP-BM5 murine leukemia virus to cause MAIDS. Treatment with GL supplemented with glycine and cysteine (Stronger Neo-Minophagen C, SNMC) was then begun on day 0 or 4 wks after virus inoculation. SNMC was administered three times a week for up to 19 wks. Immunological abnormalities were monitored with respect to the surface phenotype identified by two-color staining for CD3 and IL-2 receptor beta-chain. All mice infected with the virus alone developed MAIDS and died by 14 wks after infection. The immunopathogenesis was estimated to be an abnormal expansion of intermediate CD3 cells (i.e., extrathymic T cells) as well as other types of lymphocytes. SNMC did not change the total mortality rate. However, some mice that began the treatment on day 0 or 4 wks after infection survived 3 wks longer. Splenomegaly and lymphadenopathy in such mice were suppressed. These mice showed normal phenotypic features and normal responses to Con A. These results suggest that SNMC is effective in some MAIDS mice in preventing the progression of disease. When lymphocytes isolated from the liver, spleen and lymph nodes of diseased mice were cultured in vitro, they showed a spontaneous proliferation. Interestingly, such proliferation was inhibited by addition of liver lymphocytes, but not splenic lymphocytes, obtained from normal or SNMC-treated mice. Since liver lymphocytes contains intermediate CD3 cells with autoreactivity, they may possibly suppress the progression of disease.
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PMID:Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murine retrovirus and mechanisms involved in the prevention of disease progression. 901 40

Interleukin-2 (IL-2) receptor gamma chain-deficient mice with a truncated mutation showed the absence or severe reduction of natural killer cells, decreased numbers of T- and B-cells, marked hypoplasia of the thymus and peripheral lymphoid tissues, defective formation of lymphoid follicles and germinal centre in the peripheral lymphoid tissues, and the absence of Peyer's patches in the intestinal mucosa. In addition, marked splenomegaly with extramedullary haematopoiesis, increased level of IgM and decreased levels of IgG and IgE in serum, severe reduction of conventional B cells (B-2) in the peripheral lymphoid tissues, the presence of IgM-producing CD5+ B cells (B-1) and their differentiation into plasma cells and Motto cells in the spleen, and increased production and differentiation of macrophages in various tissues were found in the mutant mice. However, the development of both marginal metallophilic macrophage populations in the spleen and of their related macrophages in the other tissues of the mutant mice was severely impaired. All these abnormalities seem to be induced by the loss-of-function of the IL-2 receptor gamma chain. From 8 weeks of age on, inflammatory changes occurred in the intestines, mesenteric lymph nodes, lungs, liver, and kidneys of the mutant mice. Besides the absence of Hassall's corpuscles, thymic cysts were frequently observed in the mutant mice. These pathological abnormalities suggest that the gamma chain is implicated not only in lymphoid and haematopoietic development but also in thymic epithelial cell ontogeny.
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PMID:Lymphohaematopoietic abnormalities and systemic lymphoproliferative disorder in interleukin-2 receptor gamma chain-deficient mice. 930 21

The clinical histopathological and immunophenotypic features in 5 patients with Ki-1 positive non-Hodgkin's lymphoma (NHL) were studied. When first seen, 4 patients presented enlargement of superficial lymph nodes, with skin lesions in 2 patients. Two patients in stage IV with fever, hepato-splenomegaly and bone marrow invasion, died. Histologically, the tumor cells showed diffused or patchy hyperplasia. The cells were relatively large in size, rich in bosophilic or slightly eosinophilic cytoplasm with irregularly-shaped nuclei, prominent nucleoli, and distinct anaplasia and pleomorphism. Some of the cells looked very much like the Reed-Sternberg cells. Multinucleated giant cells were seen. Immunophenotypically, all the cells were CD30 (Ki-1) and CD25 (IL-2 receptor) positive but CD15 (Leu M1) negative. Thus, the 5 patient T Ki-1 positive NHL were all of T cell type.
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PMID:[Studies of the characteristic features of Ki-1 positive non-Hodgkin's lymphoma]. 938 28

Many cytokines activate two highly homologous Stat proteins, 5a and 5b. Mice deficient in both genes lack all growth hormone and prolactin functions but retain functions associated with cytokines such as erythropoietin. Here, we demonstrate that, while lymphoid development is normal, Stat5a/b mutant peripheral T cells are profoundly deficient in proliferation and fail to undergo cell cycle progression or to express genes controlling cell cycle progression. In addition, the mice lack NK cells, develop splenomegaly, and have T cells with an activated phenotype, phenotypes seen in IL-2 receptor beta chain-deficient mice. These phenotypes are not seen in mice lacking Stat5a or Stat5b alone. The results demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2 signaling in T cells.
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PMID:Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. 1007 77

We report the development of an in vivo system to induce the generation, and study the potential role, of autoantibodies to the lymphokine interleukin-2 (IL-2). To elicit IL-2 autoantibodies, mice were immunized with purified fusion proteins containing the N-terminal region of different IL-2 allotypes, where major changes have been observed. This part of the IL-2 molecule includes a conserved sequence with an essential residue for interacting with the beta-chain of the heterotrimeric IL-2 receptor. Mice bearing an RF IL-2 allotype, immunized with several N-terminal IL-2 fusion proteins, produced IgG antibodies against Mus musculus, C57BL/6, Mus spretus and the self molecule RF IL-2, but there were large differences among then in reactivity. These N-terminal IL-2 immunogens break the maintenance of self tolerance possibly by the introduction of new T cell epitopes on self IL-2. The immunized mice developed a complex set of immunopathologies such as splenomegaly, haemolytic anaemia and lymphoadenopathy with a long latency period after the last immunization. These pathologies resembled those described for IL-2-deficient mice (IL-2(-/-)) and mice injected with anti-IL-2 receptor alpha-antibody. Human IL-2 autoantibodies have been detected in several immune-affected situations and therefore this model would be of interest to study the potential evolution of these autoantibodies in relation to immunopathology. The production of these autoantibodies against conserved epitopes of mouse IL-2 may facilitate studies on the structural homologies between different IL-2 allotypes and from various species, and could be applied to other cytokines.
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PMID:Induction of autoantibodies to different interleukin-2 allotypes. 1022 31

A 45-year-old woman was admitted to our hospital in August, 1999. Laboratory data showed a white blood cell count of 5,050/microliter with 78% abnormal lymphocytes, hemoglobin 6.8 g/dl, platelets 4.8 x 10(4)/microliter, and soluble IL-2 receptor 97,600/ml. The abnormal cells were characterized by a hairy appearance under phase contrast microscopy, and showed strong tartrate-resistant acid phosphatase activity. Immunophenotype analysis revealed that these cells were positive for CD11c, CD19 and CD25, and negative for CD5. Bone marrow biopsy showed diffuse proliferation of hairy cells with moderate myelofibrosis. We diagnosed the patient as having European-American-type hairy cell leukemia. Pentostatin was administered at a dose of 5 mg/m2 weekly. After twelve doses, the peripheral blood data returned to the normal range with no hairy cells in the blood or bone marrow, although slight splenomegaly remained. The patient underwent splenectomy in December of the same year, and we were unable to find any hairy cells by histological and immunohistochemical examination. Although most patients with hairy cell leukemia in Japan have the Japanese variant, and the European-American type is rare, pentostatin is as effective as it is for European and American patients.
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PMID:[Successful treatment of hairy cell leukemia with pentostatin]. 1152 43

In patients with ALPS, defective homeostasis of lymphocytes is reflected in abnormal accumulation of lymphocytes, leading to lymphadenopathy, (hepato)splenomegaly and hypersplenism, autoimmunity due to a failure to remove autoreactive lymphocytes, and inappropriate survival of lymphocytes associated with an increased occurrence of lymphoma. Several of the laboratory findings are unique for ALPS and reflect defective Fas-mediated apoptosis and abnormal immune regulation. Much has been learned about the molecular mechanisms that underlie defective Fas-mediated apoptosis and the complex relationship between genotype, phenotype and disease penetrance. Family studies strongly suggest the contribution of one or more additional factors to the pathogenesis of ALPS. This may pertain to defective immunoregulation by an altered IL-2/IL-2 receptor system, reflected in the specific loss of CD4+/CD25+ T cells, and/or by the highly increased IL-10 levels, but other factors may equally be involved. Treatment strategies remain mostly targeted at the disease manifestations, but more specific therapies directed at the primary pathogenic defects themselves might become possible in the future. Continued efforts directed at both careful clinical follow-up and basic scientific investigation are needed to increase our understanding of the incidence, natural history, and pathogenesis of ALPS. In return, this may prove of benefit for the understanding of autoimmune disease in general.
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PMID:Autoimmune lymphoproliferative syndrome (ALPS). 1257 Aug 31

A 48-year-old man infected with an HIV-1 experienced intermittent bouts of fever, lymphadenopathy, elevated CRP level, and thrombocytopenia, each lasting about 2 weeks, and recurring at 2-3 month intervals. His CD4 count was about 500/microL, and he had never received antiretroviral therapy (ART). In March 2005, he experienced the same symptoms, accompanied by liver damage, splenomegaly, pleural fluid, and a high serum soluble IL-2 receptor level. Examination of a cervical lymph node specimen resulted in a diagnosis of Castleman disease, plasma cell type. Immunohistochemical studies confirmed the presence of HHV-8 and Ebstein-Barr virus (EBV). Since the plasma HHV-8 DNA and serum IL-6 were elevated during the flare-up, were negative between episodes, he was treated with ART to control the Castleman disease. He remained asymptomatic for 3 months, but, similar symptoms recurred with a high level of HHV-8 DNA in his PBMCs. Oral valganciclovir was them started at 1,800 mg twice daily, and his symptoms immediately improved. The HHV-8 DNA level in the PBMCs decreased markedly over the course of 4 weeks, and valganciclovir was discontinued. One week later, he experienced another flare-up, and was successfully treated with 10 days of valganciclovir 1,800 mg, followed by maintenance with valganciclovir 900 mg. ART was discontinued, because the valganciclovir plus ART caused severe fatigue. No subsequent flare-ups have been observed, and, no HHV-8 DNA has been detected in his PBMCs. Castleman disease is an unusual complication in patients with HIV-1 and HHV-8 infection, but it should be included in the differential diagnosis of patients who exhibit a relapsing systemic inflammatory syndrome and lymphoadenopathy. Further study is needed to determine the appropriate usage and timing of the anti-HHV-8 and HIV-1 medication.
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PMID:[A case of HIV-1 and HHV-8-associated Castleman disease with a relapsing high fever and lymphoadenopathy]. 1692 87


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