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)

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
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PMID:Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. 815 60

Aging in humans is associated with the decline of functional activities of the GH-insulin-like growth factor I (IGF-I) axis and the immune system. Because lymphocytes express GH-IGF-I, as well as GHRH and their respective receptors, restoration of this axis in age-advanced individuals, by the administration of GHRH, may enhance immune cell function. This hypothesis was tested by a single blind randomized placebo-controlled trial of 5 months duration, in which healthy elderly subjects (10 women, 9 men) self-administered sc nightly placebo for 4 weeks, followed by 16 weeks of [norleucine27]GHRH (1-29)-NH2 at a dose of 10 micrograms/kg. Fasting (0800 h-0900 h) blood samples were obtained for immune studies and for measurements of serum concentrations of IGF-I and soluble interleukin (IL)-2 receptor. GH pulsatility was determined in blood samples obtained at 10-min intervals for 12 h (2000 h-0800 h). Freshly isolated peripheral lymphocytes were analyzed by flow cytometric analysis for determination of lymphocyte subsets and monocytes. Mitogen stimulation responses, natural killer cell number and cytotoxicity, basal and stimulated IL-2 secretion from cultured lymphocytes, and IL-2 and IL-2R messenger RNA expression were measured. These studies were conducted at baseline, after placebo, and during GHRH analog administration at 4 and 16 weeks. Treatment with GHRH analog resulted in a significant increase (107 and 70% in men and women, respectively) in the 12-h integrated GH secretion (P < .05) and serum IGF-I levels (28%) (P < .001) in both men and women by 4 weeks and lasted 12 weeks for IGF-I and 16 weeks for GH. Activation of the immune system occurred in both sexes within 4 weeks. A 30% increase (P < .001) in lymphocytes expressing the transferrin receptor (CD71) and in monocytes (CD14) (P < .05) occurred within 4 weeks. By 16 weeks, there was a significant increase (30%) in B cells (CD20) (P < .01), in cells expressing the T cell receptor alpha/beta (20%) (P < .01), and T cell receptor gamma/delta (40%) (P < .0001). There were no changes in the number of T cells (CD3), T cell subsets (CD4, CD8), or natural killer cell (CD57) over the treatment period. The increase in B cell number was associated with enhanced responsiveness (50%) to the B cell mitogens: pokeweed mitogen (P < .01 or better) and Staphylococus aureus cells (P < .001), and a transient increase at 4 weeks in circulating IgG (P < .0001), IgM, and IgA (P < .001). T cells were functionally activated, as evidenced by a 50% increase in responsiveness to phytohemagglutinin (P < .01 or better), 70% increase in the number of lymphocytes expressing the IL-2 receptor (IL-2R) (CD25) (P < .001), and enhanced IL-2R messenger RNA expression and basal IL-2 secretion (50%) (P < .05) at 16 weeks of treatment. Furthermore, circulating soluble IL-2 receptor rose significantly (15%) (P < .05) within 4 weeks of treatment and remained elevated for the duration of the study. There were no sex differences in the immune response to GHRH analog and no adverse effects. These results indicate that GHRH analog administration has profound immune-enhancing effects and may be of therapeutic benefit in states of compromised immune function.
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PMID:Effects of [norleucine27]growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women. 936 May 12

Malignant histiocytosis (MH)-like B-cell lymphoma (BCL) is a neoplastic proliferation of large B cells clinically characterized by fever, hepatosplenomegaly, haemophagocytosis and abnormal laboratory data, without lymphadenopathy or skin lesions. Interestingly, most cases have been reported in Asian patients, and it is unclear whether MH-like BCL is biologically distinct from conventional large B-cell lymphomas. We report five Japanese patients with MH-like BCL. Biopsied specimens of bone marrow, liver and/or spleen showed infiltration of neoplastic B cells accompanied by haemophagocytosing histiocytes. Lymphoma cells were positive for CD19, CD20 and HLA-DR surface antigens, and negative for CD5 and CD10. In four cases elevated serum levels of interleukin (IL)-6 and the soluble IL-2 receptor isoform were noted, but not IL-1beta, IL-2 or tumour necrosis factor-alpha. Autopsies of two cases were pathologically diagnosed as intravascular lymphomatosis (IVL). Based on these observations, the current and nine previous cases reported as MH-like BCL in Japan were re-evaluated. They appear to form a peculiar variant of IVL, characterized by bone marrow involvement at presentation, haemophagocytic syndrome, and a rapidly aggressive clinical course, but rarely neurological complications or skin lesions. This variant may merit separate consideration because of the problems posed in the initial diagnosis and therapeutic approaches.
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PMID:Malignant histiocytosis-like B-cell lymphoma, a distinct pathologic variant of intravascular lymphomatosis: a report of five cases and review of the literature. 940 Oct 80

Numerous interactions exist among the nervous, endocrine and immune systems, mediated by neurotransmitters, hormones and cytokines. The function of these systems shows patterns of circadian rhythmicity and a number of age-related changes in the 24-hour hormonal and nonhormonal rhythms have been found in older human beings. The aim of this study was to evaluate the presence of altered integration among the nervous, endocrine and immune systems in older adults. Cortisol, melatonin, thyrotropin-releasing hormone (TRH), thyroid-stimulatinghormone (TSH), free thyroxine (FT4), growth hormone (GH), insulin-like growth factor I (IGF-I) and interleukin 2 (IL-2) serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from seven healthy young subjects aged 36-58 years (mean age +/- s.e. 45.28 +/- 3.31) and from seven healthy old subjects aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.91). There was a statistically significant difference between the groups in the observed values of CD20 (total B cells, higher in the young subjects, t = 2.48, P = 0.028) and CD25 (activated T cells with expression of the alpha chain of IL-2 receptor, higher in elderly subjects, t = -2.23, P = 0.045); DR+ T cells were also higher in elderly subjects, T=34.0, P=0.01). There was no statistically significant difference in the observed values of CD2(total T lymphocytes), CD4 (helper/inducer T cells), CD8 (suppressor/cytotoxic T cells), CD4/CD8 ratio, CD16 (natural killer cells), HLA-DR (B cells and activated T cells), TcR delta 1 (epitope of the constant domain of delta chain of T-cell receptor 1), cortisol, melatonin, TRH, TSH, FT4" GH, IGF-I, IL-2. In the group of younger subjects a clear circadian rhythm was validated for the time-qualified changes of all the factors studied, with the exception of CD16, FT4 and IL-2. In the group of elderly subjects a clear circadian rhythm was validated for the nyctohemeral changes of CD2 (with a phase delay of three hours), CD8, CD4/CD8 ratio, CD16, CD25 (in opposite phase), cortisol (with a phase delay of one hour), melatonin, TSH (with a phase delay of one hour) and GH (with a phase advance of one hour). The results of the current study show that aging is associated with enhanced responsiveness of the T cell compartment and alterations in temporal architecture of neuro-endocrine-immune system.
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PMID:Age-related changes of neuro-endocrine-immune interactions in healthy humans. 958 14

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

This article focuses on the recent dramatic advances in the applications of monoclonal antibody therapy to hematopoietic and neoplastic disease. The increase in the understanding of the role of growth factors and their receptors in the pathogenesis of malignancy and other undesirable hematological events taken in conjunction with the ability to produce humanized chimeric monoclonal antibodies to these targets is providing a new perspective for the treatment of leukemia, lymphoma and breast cancer, autoimmune disease and for prevention of ischemic complications. Dr. Waldmann describes approaches targeting the Her2/neu and the II-2/IL-15 receptor systems. The Her2/neu receptor is overexpressed in select breast, ovarian, gastric and pancreatic neoplasms. The use of trastuzumab (Herceptin) in the treatment of patients with breast cancer whose tumors overexpress this receptor are reviewed. The IL-2 receptor (Tac) is expressed on select malignant cells (adult T cell leukemia, hairy cell leukemia) and activated T cells involved in autoimmune disease and organ rejection. Humanized anti-Tac alone (daclizumab, Zenapax) or armed with toxins or radionuclides have been used successfully in the treatment of leukemia. Dr. Levy updates the experience with rituximab targeting CD20 on B cell lymphomas and reviews the antibodies to CD3, CD22, CD33, CD52, HLA-DR beta chain and HLA-D currently in or proposed for clinical trials, including radiolabelled antibodies. In the last section, Dr. Coller reviews the therapeutic results achieved with abciximab (ReoPro), an antagonist of platelet receptor GPIIbIIIa for the prevention of restenosis in percutaneous coronary interventions and the treatment of unstable angina. The mechanism of action, pharmacology and safety and efficacy of abciximab are reviewed.
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PMID:Emerging Therapies: Spectrum of Applications of Monoclonal Antibody Therapy. 1170 53

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

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

The immune system plays an important role in the defense against neoplastic disease and immune responses show temporal changes related to circadian variations of antibodies, total lymphocytes in the peripheral blood and cell mediated immune responses. In this study we evaluate. lymphocyte subpopulations and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at four-hour intervals for 24-hours starting at 06.00 h from ten healthy subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve, mean diurnal levels (mean of 06.00-10.00-14.00 h) and mean nocturnal levels (mean of 18.00-22.00-02.00 h) were calculated, and the presence of circadian rhythmicity was evaluate. When we compared AUC values there was a decrease in CD8bright (T suppressor subset) and an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic subset) and CD8bright levels were lower, and CD16 levels were higher in cancer patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B activated lymphocytes with expression of the a chain of IL-2 receptor) levels were higher, while CD8, CD8bright, CD20 (total B-cells), TcRd1 (epitope of the constant domain of d chain of T-cell receptor 1) and dTcS1 (epitope of the variable domain of d chain of T-cell receptor1) levels were lower in cancer patients. A clear circadian rhythm was validated for the time-qualified changes in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8 bright, CD8 dim, CD16, TcRd1 and dTcS1 with acrophase in the morning in the control group. A clear circadian rhythm was validated for the time-qualified changes in CD4 with acrophase at night, in the group of cancer patients. Results obtained in our study show that lung cancer is associated with anomalies of proportion and circadian variations of lymphocyte subsets that must be considered when adoptive immunotherapy has to be planned.
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PMID:Immune system alterations in lung cancer patients. 1279 8


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