Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Many studies illustrate that physical or psychologic stressors can alter human immune function, which might predispose one to an increased susceptibility to infections. In the present study, we monitored immune responsiveness in 16 first-year medical students (age 23.8 +/- 2.2 years) during the first examination session. Baseline blood samples were collected 30 days prior to the first examination session. Subsequently, subjects were randomly assigned to two groups, and blood samples were collected at 24 h (POST24h) or 48 h (POST48h) after an examination. The percentage of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD45RO(+), CD3(+)CD45RA(+), CD3(-)CD16(+)56(+), CD19(+), and CD14(+) cells in whole blood was examined to determine changes in circulating immune cell populations. Activation of peripheral blood mononuclear cells (PBMC) with a mixture of phorbol myristate acetate (PMA) and ionomycin or lipopolysaccharide (LPS) for 4 h was used to assess the distribution of interleukin-2 (IL-2)-secreting or interferon-gamma (IFN-gamma)-secreting CD4(+) and CD8(+) cells, as well as IL-1alpha-secreting CD14(+) cells. Activation with a combination of phytohemagglutinin (PHA) and LPS was used to assess secretion of IL-2, IFN-gamma, IL-4, IL-10, soluble IL-2 receptor-alpha (sIL-2Ralpha), IL-1beta, and IL-1R antagonist (IL-1Ra) by PBMC in 48-h cell culture. A significantly higher level of total T cells was found at POST24h, and CD14(+) was elevated at both POST24h and POST48h. The percentage of CD4(+) and CD8(+) cells significantly declined at POST24 and POST48h. A significant elevation in the percentage of memory T cells was observed at POST48h, whereas the percentage of naive T cells was elevated at POST24h and POST48h. These changes were accompanied by a significant decline in percentage of natural killer (NK) cells 24 h after the examination. The percentage of IL-2-producing CD4(+) and CD8(+) cells was significantly lower at POST24h, and the percentage of CD8(+)IFN-gamma(+) cells significantly declined at POST48h. The percentage of CD14(+)IL-1alpha(+) significantly declined at both POST24 and POST48h. A significant decrease was observed in IL-2 secretion 24 h after the examinations, and the secretion of IL-4 and IL-1beta significantly declined at POST48h. No changes in IFN-gamma, IL-10, sIL-2Ralpha, and IL-1Ra secretion were observed. We conclude that the stress outcomes of academic examinations in first-year medical students can significantly alter immune cell distribution and in vitro production and secretion of specific cytokines.
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PMID:Immune responsiveness following academic stress in first-year medical students. 1157 63

The present study evaluated the contribution of some peripheral immunological parameters and GFAP immunoreactivity at different ontogenic stages of non convulsive absence epilepsy in WAG/Rij rats. For this, 2- and 6-month-old WAG/Rij rats, and the aged-matched control Wistar-albino rats were used. After collecting blood samples from all rats, the CD3 + (T cells), CD4 + (T helper), CD8 + (T cytotoxic), CD19 + (B cells) and CD25 + (IL-2 receptor, active T cell) cell ratios were determined by indirect immunofluorescence method and, serum IgG, IgA, IgM levels were evaluated by using rat radial immunodiffusion plates. After decapitation, brains were dissected and, GFAP staining was evaluated in the areas of caudate nucleus, thalamus, hippocampus, amygdala and cerebellum by immunohistochemistry. CD3 + cells and IgM levels increased with age in WAG/Rij rats. However, GFAP + astrocytes were decreased with age in caudate nucleus, thalamus, amygdala, and cerebellum of WAG/Rij rats. In the genetically absence epileptic rats, the humoral immunity was found to be affected more and activated by age. Additionally, astrocytes in thalamus and caudate nucleus that are the most important areas in the pathogenesis of absence epilepsy, were found to be decreased with age in WAG/Rij rats. From the results, it can be concluded that peripheral immunological parameters together with astrocytic activity may participate in the etiopathogenesis of absence epilepsy.
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PMID:Age dependent changes in some immune system parameters and GFAP immunoreactivity in genetically absence epileptic rats. 1169 32

Chronic lymphocytic leukemia (CLL) is a phenotypically distinguishable form of B-lymphoid leukemias. The regularity of surface membrane antigen expression patterns, their interrelationships as well as the effects of the three frequent chromosomal aberrations, ie 11q deletion, 13q deletion and trisomy 12, were investigated in 35 classic CLL cases by flow cytometry. The two-way cluster analysis of 31 individual antigens revealed three expression patterns: (1) most cells in most cases positive (CD5, CD19, CD20, CD23, CD27, CD40, CD45, CD45RA); (2) most cells in most cases negative (CD10, CD14, CD34, CD122, CD154, mIgG); and (3) a mixed pattern with a variable number of positive cases and a variable percentage of positive cells in individual cases (CD11c, CD21, CD22, CD25, CD38, CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, mIgD, mIgkappa, mIglambda, mIgM). The expressions of several antigens were strongly interdependent, even when antigens belonged to entirely different gene families. Such antigen pairs were: CD11c/CD21; CD19/CD45; CD19/CD79b; CD22/CD45RA; CD23/Igkappa; CD25/mIgM; CD27/CD45; CD45/CD79b; CD45RA/Igkappa. In contrast, the expression of some antigens was mutually exclusive, the best examples being CD45RA/CD45RO, CD38/CD80 and CD45RA/CD80. Deletion of chromosome arm 11q attenuated expression of splicing variant CD45RA, but enhanced CD45RO expression. In contrast, cases of trisomy 12 were associated with enhanced CD45RA and attenuated CD45RO expression. Similarly, trisomy 12 was associated with enhanced CD27 and mIgkappa expression. The variable levels of signaling surface membrane antigens, their interactions and interference by genetic aberrations are likely to affect the clinical progression and drug response of CLL.
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PMID:Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities. 1184 Feb 83

The factors determining the growth and survival of cells in B chronic lymphocytic leukemia (CLL) have remained poorly understood. We investigated the effects of optimal mitogen combinations (OMCs) on the expression of 26 surface membrane antigens among 33 CLL patients. The seven OMCs used were selected after pre-testing 14 combinations of (1) S. aureus Cowan I (SAC), (2) interleukin-2 (IL-2), (3) tumor necrosis factor alpha (TNF-alpha) and (4) 12-O-tetradecanoylphorbol 13-acetate (TPA; also known as phorbol 12-myristate 13-acetate or PMA). In flow cytometry we revealed that OMCs induced statistically highly significant upregulation of the expression of CD5, CD11c, CD19, CD22, CD23, CD25, CD38, CD40, CD45, CD45RO, CD95, CD126, CD130 and FMC7, and downregulation of CD20 and CD124 expression. Interestingly, the expression of CD27, CD45RA, CD79b, CD80, CD122 and that of the immunoglobulin gene superfamily members CD21, Ig-kappa, Ig-lambda, Ig-delta and Ig-micro were not significantly affected under similar conditions. The expression of several antigens was co-regulated, suggesting common regulatory pathways. These antigens include CD11c/CD5, CD11c/CD22, CD11c/CD126, CD11c/FMC7 as well as CD27/CD45, CD27/CD45RA and CD27/CD79b. Upregulation of surface antigen expression, induced by OMCs, should be applicable in antibody therapy in vitro and in vivo, and in negative stem cell selection for autotransplantation. Furthermore, the current strategy to enhance cell surface antigen expression may be a versatile tool to raise humoral and cell-mediated host defense against CLL cells. Upregulation of proteins mediating positive growth signals (eg CD25, CD40) and negative signals or apoptosis (eg CD95) may be used to sensitize cells to chemotherapy and programmed cell death.
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PMID:Surface membrane antigen expression changes induced in vitro by exogenous growth factors in chronic lymphocytic leukemia cells. 1220 Jun 83

This study addressed several questions concerning age-related changes in human B lymphopoiesis. The relative abundance of pro-B, pre-B, immature, naive, and mature B cells among the CD19(+) lymphocyte fraction of human bone marrow was found not to change appreciably over the interval between 24 and 88 years of age. Moreover, proliferation of pro-B and large pre-B cells in adult marrow equaled that observed with fetal marrow specimens. Exceptionally low numbers of lymphocyte precursors were found in some marrow samples, and the values obtained were used to determine parameters that best reflect B lymphopoiesis. Cord blood always contained higher incidences of functional precursors than adult cells. However, sorted CD34(+) Lin(-) CD10(+) progenitors from cord blood and adult marrow had equivalent potential for differentiation in culture, and notable age-related changes were found in more primitive subsets. A recently described subset of CD34(+)CD38(-)CD7(+) cord blood cells had no exact counterpart in adult marrow. That is, all adult CD34(+)Lin(-)CD7(+)CD10(-) cells expressed CD38, displayed less CD45RA, and had little B-lineage differentiation potential. The CD7(+) fractions in either site contained progenitors for erythroid and natural killer (NK) lineages, and ones sorted from marrow expressed high levels of transcripts for the CD122 interleukin 2 (IL-2)/IL-15 receptor required by NK-lineage precursors. Dramatic changes in human B lymphopoiesis occur early in life, and more information is required to construct a probable sequence of differentiation events prior to the acquisition of CD10.
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PMID:B lymphopoiesis is active throughout human life, but there are developmental age-related changes. 1239 2

Recent studies have demonstrated that B-cell chronic lymphocytic leukemia (CLL) consists of two clinical entities with either somatically hypermutated (M-CLL) or unmutated (UM-CLL) immunoglobulin variable heavy-chain (VH) regions. In view of the fact that the cellular biology of these two subsets of disease is currently unexplored, we performed an extensive analysis of the surface antigen expression and correlated this with the VH gene mutation status in a cohort of 32 CLL patients. Using polymerase chain reaction amplification and nucleotide sequencing, the VH genes were shown to be mutated in 10 cases (31%) and unmutated in 22 (69%). The expression of 27 surface membrane antigens in peripheral blood leukemic cells was analyzed by flow cytometry, measuring both the percentage of positive cells as well as the geometric mean fluorescence intensity (GMF). Most of the surface membrane antigens (CD5, CD11c, CD19, CD20, CD21, CD22, CD23, CD25, CD40, CD45, VD79b, CD80, CD95, CD122, CD124, CD126, CD130, CD154, IgM, and IgD) showed a similar expression pattern in both UM-CLL and M-CLL patients. The similarity of M-CLL and UM-CLL, as demonstrated here for the first time with many protein markers, indicates a considerably homogeneous phenotype in both subsets. Furthermore, CD27 was strongly expressed in all cases, which may suggest a memory cell phenotype for both M-CLL and UM-CLL. More positive cells in the UM-CLL group were observed regarding CD38, but CD38 was not a good predictor of VH gene mutation status. Seventy percent of the M-CLL cases, but only 36% of UM-CLL cases, were Ig-lambda+. The most striking differential expression, however, was observed in the two slicing variants of the common leukocyte antigen CD45, namely CD45RO and CD45RA. CD45RO expression was significantly associated with M-CLL, whereas the GMF intensity of CD45RA tended to be associated with UM-CLL. The role of these CD45 splicing variants in the pathogenesis of CLL deserves further investigation.
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PMID:Surface antigen expression and correlation with variable heavy-chain gene mutation status in chronic lymphocytic leukemia. 1263 Dec 59

We conducted a non-randomised controlled phase II trial to investigate the role of preoperative administration of interleukin-2 (IL-2) in patients with renal cell carcinoma undergoing tumour nephrectomy. A total of 120 consecutive patients were allocated alternately to the two study groups: perioperative immunomodulation with IL-2 (IL-2 group; n=60) and perioperative immunomonitoring without immunomodulation (control group; n=60). Patients from the IL-2 group received four doses of 10 x 10(6) IU m(-2) twice daily subcutaneously a week before operation followed by a daily maintenance dose of 3 x 10(6) IU m(-2) subcutaneously until a day before the operation. Parameters of cellular and humoral immunity (leucocytes, T-cell markers CD3, CD4, and CD8, B-cell marker CD19, monocyte marker CD14, natural killer (NK) cell markers CD16, CD56, and CD57, activation markers CD6, CD25, CD28, and CD69, progenitor cell marker CD34, as well as IL-2, IL-6, IL-10, soluble IL-2 receptor, IL-1 receptor antagonist, transforming growth factor-beta1, and vascular endothelial growth factor) were measured in peripheral venous blood at various intervals. Interleukin-2-related toxicity was WHO grade 1 (24%), 2 (67%), and 3 (9%). In the postoperative period, T-cell markers, activation markers, and NK cell markers decreased, and IL-6 and IL-10 increased. However, all these alterations were significantly less accentuated in patients who had been pretreated with IL-2. Median follow-up was 40 months. Tumour-specific survival in the IL-2 group and the control group was 98 vs 81% after 1 year and 86 vs 73% after 5 years (P=0.04). A similar effect was found for progression-free survival. We conclude that IL-2 can be safely administered in the perioperative period and modulates immunological parameters. However, to validate the survival data, a larger randomised phase III trial is needed.
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PMID:Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial. 1703 3

Myasthenia gravis (MG) is caused by T-cell-dependent autoantibodies against muscle acetylcholine receptors (AChR) at the neuromuscular junction. Here, we adopted ELISA and flow cytometry techniques to measure the levels of Th1, Th2, Th3 cytokines, inflammatory cytokine and chemokine sICAM-1 and to analyze the phenotypes of CD4(+) and CD8(+) regulatory cells as well as the expression of BAFF-R on CD19(+) B cells in peripheral blood from 75 MG patients and 50 healthy controls. There were no differences in the levels of IL-2, IL-4, IL-10, IL-13, IFN-gamma, TNF-alpha, TGF-beta and sCTLA-4 in both sera and culture supernatants between MG patients and healthy controls. The level of IL-12 was decreased in culture supernatants from MG patients, and the level of sICAM-1 was increased in both sera and culture supernatants from MG patients. Although the populations of CD8(+)CD28(-) and CD8(+)CD122(+) regulatory T cells were not different between MG patients and healthy controls, MG patients exhibited the decrease of CD4(+)CD25(high)Foxp3(+) regulatory T cells and the increase of CD19(+)BAFF-R(+) B cells, revealing that MG patients should display the dysfunction of T cell balance and the activation of B cell maturation.
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PMID:Decrease of CD4(+)CD25(high)Foxp3(+) regulatory T cells and elevation of CD19(+)BAFF-R(+) B cells and soluble ICAM-1 in myasthenia gravis. 1805 87

Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a strategy that appears to be conserved between at least EBV and MHV68.
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PMID:The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation. 1838 62


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