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 Fc gamma RIII receptor (CD16) has been described on natural killer cells and a small subset of T lymphocytes. CD16+bright lymphocytes represent the typical population of peripheral blood CD3- NK cells. In these studies in addition to CD16+bright NK cells Fc gamma RIII expressing cytotoxic T lymphocytes in peripheral blood from one healthy individual are characterized as CD16+dim non-MHC-restricted CTLs either expressing the alpha/beta (80%) or the gamma/delta T cell receptor (20%). Both CD16+ subsets are clearly distinct in their functional capacity performing NK and ADCC activity. Freshly isolated CD16+dim T cells exert higher ADCC, CD16+bright NK cells higher NK activity. They are also differentially activated by interleukin-2 since CD16+bright NK cells reveal a bright expression of the p75 IL-2 receptor beta-chain in contrast to the very low p75 expression on CD16+dim T cells. This activation leads to a gradual increase of ADCC by NK cells. Finally the CD16 expression pattern with low and bright intensity represents a stable phenotype expressed by clones generated from these different subpopulations. On a clonal level CD16+dim non-MHC-restricted T cells can be distinguished from CD16+bright NK cells by their lower capacity in NK killing, but they are equally potent in ADCC. Finally these CD3+CD16+dim clones provide the basis for studies of Fc gamma RIII and TcR interaction.
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PMID:Analysis of CD16+dim and CD16+bright lymphocytes--comparison of peripheral and clonal non-MHC-restricted T cells and NK cells. 139 40

The expression of a range of surface molecules/receptors that are important in the host response to infection and foreign antigens was examined using peritoneal macrophages isolated from patients on continuous ambulatory peritoneal dialysis (CAPD) with peritonitis. The macrophage phenotypic profile was compared with that of normal peripheral blood monocytes. Consistently there was increased expression by macrophages of CD14, ICAM-1 (CD54), Fc gamma RI (CD64), Fc gamma RII (CDw32), Fc gamma RIII (CD16), transferrin receptors (CD71) and tissue factor. Increased expression of MHC class II was marginally significant. There was no detectable expression of either the p55 (CD25) or p70 chains of the IL-2 receptor. The expression of the complement receptors, CR1 (CD35) and CR3 (CD11b, CD18), was reduced. The activity of well-known inflammatory cytokines, rather than uraemic molecules, can account for the phenotypic profile of these extravasated peritoneal macrophages. The results of this study indicate that peritoneal macrophages from CAPD patients with peritonitis display a phenotype consistent with them being in vivo-derived inflammatory macrophages, and that they are appropriate for use in studies of anti-inflammatory agents.
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PMID:Peritoneal macrophages during peritonitis. Phenotypic studies. 160 34

Mitoxantrone (DHAD), an anthracenedione with antineoplastic properties similar to doxorubicin, was tested for therapeutic efficacy and for immunomodulating action on lymphocyte subsets in 16 metastatic breast cancer patients, 12 of whom had been previously treated with chemotherapy. DHAD was given intravenously at a dose of 14 mg/m2 every 21 days. To evaluate total T lymphocytes (CD3), T helper (CD4), and T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio, venous blood samples were drawn before and after the first DHAD cycle. Moreover, in 8/16 patients, B lymphocytes (CD20), T suppressor cells (CD8+/CD57+), T cytotoxic cells (CD8+/CD57-), NK (CD16) and IL-2 receptor-expressing cells (CD25) were also measured at the same time. An objective tumor response was achieved in 5/16 (31%) patients and the response rate was significantly higher in patients pretreated with hormone therapy alone than in those pretreated with chemotherapy. No relation was found between clinical response and changes in the CD4/CD8 ratio. Neither the mean number nor the percentage of CD3, CDA and CD8 cells observed after DHAD were significantly different with respect to those seen before. In contrast, the mean number of T suppressor cells, B lymphocytes and CD25-positive cells was significantly lower after than before DHAD administration, whereas no difference was seen in NK cells. These results confirm in humans the immunomodulating properties of DHAD previously described in experimental conditions. However, the DHAD-induced changes in lymphocyte subsets do not seem to be related to the clinical response in breast cancer.
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PMID:Mitoxantrone as a single agent in pretreated metastatic breast cancer: effects on T lymphocyte subsets and their relation to clinical response. 186 50

In a previous study we demonstrated that cluster headache (CH) patients present an increased Natural Cytotoxic response after incubation of their peripheral blood lymphocytes (PBL) with Interleukin-2 (IL-2). This phenomenon led to an investigation of the phenotypic expression of PBL before and after IL-2 incubation, and of the IL-2 lymphocyte receptor. IL-2 receptor is expressed on T-lymphocytes activated with an high-affinity binding site. The analysis of the function of human IL-2 receptor was facilitated by the production of a specific monoclonal antibody (MAb). This MAb identifies the IL-2 receptors by blocking the binding of radiolabelled IL-2 to T-cells. In addition, we studied the expression of Leu-4, specific for T-cells; of Leu-11b, specific for FC receptor on NK cells; and the Transferrin Receptor, specific for lymphoblasts and monocytes. Twenty-three episodic CH patients were selected for this study. Ten sex and age-matched healthy volunteers were used as the control group. We evaluated the PBL phenotypic expression of cells subsets before incubation with IL-2 (1,000 I.U./ml) and after 72 hours. The following Becton Dickinson MAbs have been used: anti-Leu-4 (CD3), anti-IL-2 receptors (CD25), anti-Transferrin receptor (TFR) and anti-Leu-11b (CD16). Indirect fluorescence with a Becton Dickinson FACS-420 flow cytometer was used to analyze the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective expression of IL-2 receptors on peripheral blood lymphocytes from patients with cluster headache. 233 78

Receptors for IgG (Fc gamma R) are expressed by small subpopulations of peripheral blood T lymphocytes. Our studies demonstrate that T lymphocytes can be induced in vitro to express two different low-affinity Fc gamma R. Mitogen activation of peripheral blood T lymphocytes obtained from eight healthy individuals leads to considerable augmentation of the Fc gamma RIII+ (CD32) T cell subpopulation. The highest percentage of CD32 expressing T lymphocytes could be detected after three days of activation. The T cell subpopulation which transiently express the CD32 antigen, encompasses CD4+ and CD8+ cells. Molecular cloning of the CD32 antigen by reverse transcription and polymerase chain reaction demonstrates that activated human T lymphocytes express the Fc gamma RIIIb2 isoform. The percentage of the Fc gamma RIII+ (CD16) T cell subpopulation was significantly increased only in the lymphocyte populations obtained from three out of eight volunteers immediately after mitogen activation. However, during short-term cell culture the CD16 expressing CD8+ T cell subset increased in the T cell population from all individuals investigated. During this time, the IL-2 receptor alpha-chain (CD25) expression level decreased as a function of time. In contrast to the CD8+CD16+ T cells, the percentage of the non-MCH-restricted CD56+CD16+ T cells was not influenced by mitogen activation and time of cell cultivation. We could show that CD16 in T cells is able to mediate a stimulus leading to proliferation of the CD8+CD56-CD16+ T cells but not that of the CD56+CD16+ T cell subset. This discrepancy cannot be explained by the expression of different Fc gamma RIII isoforms, because both T cell subsets express Fc gamma RIIIA alpha, as we demonstrate in this report.
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PMID:Activation-dependent expression of low affinity IgG receptors Fc gamma RII(CD32) and Fc gamma RIII(CD16) in subpopulations of human T lymphocytes. 764 65

In this study we identify and characterize a subset of human peripheral blood T cells, present in all individuals, that has features previously described for T cells either separately or in special circumstances. These cells are found in purified suspensions of resting peripheral blood lymphocytes within the CD8+ T lymphocytes, express alpha beta T cell receptor (TCR), and can be identified and isolated because of high-density expression of surface CD11b (TCR alpha beta +/CD3+/CD8+/CD11b+ cells). They coexpress constitutively the IL-2 receptor beta chain, Fc gamma RIIIA, and CD56. Although they do not mediate spontaneous cytotoxicity, CD3+/CD8+/CD11b+ cells have cytotoxic potential, demonstrated in redirected cytotoxicity assays with P815 target cells in the presence of anti-Fc gamma RIII (CD16) or anti-CD3 monoclonal antibodies. Stimulation of CD3+/CD8+/CD11b+ cells with rIL-2 induces proliferation, cytotoxicity against NK-sensitive and NK-resistant target cells, and expression of surface activation antigens, including IL-2 receptor alpha chain (CD25). CD3+/CD8+/CD16+/CD56+ cell clones with cytotoxic functions including those mediated by engagement of surface CD16 were obtained by limiting-dilution cloning of purified CD3+/CD8+/CD11b+ cells in the presence of rIL-2 and autologous feeder cells. Our data support the hypothesis that the CD3+/CD8+/CD11b+/CD16+ cells represent a discrete peripheral blood lymphocyte subset that could be the physiological counterpart of that expanded in several pathological conditions and in large granular lymphocyte lymphocytosis.
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PMID:Coexpression of Fc gamma receptor IIIA and interleukin-2 receptor beta chain by a subset of human CD3+/CD8+/CD11b+ lymphocytes. 768 65

Lymphocytes and their subset counts were determined in 30 cardiac surgery patients during cardiopulmonary bypass (CPB) with or without use of an autotransfusion device. In the autotransfusion group, centrifuged and washed autologous red blood cells (median 400 mL [range 200-770 mL]) and in the control group corresponding amounts of homologous packed red blood cells (median 500 mL [range 250-750 mL]) were transfused after declamping the aorta. The percentages of T lymphocytes (CD3) and T cytotoxic cells (CD8) increased in both groups (CD3 up to 5%, P < 0.05 and CD8 up to 35%, P < 0.01), but the percentage of T helper cells (CD4) did not change. The ratio of CD4/CD8 cells decreased (up to 34%, P < 0.01). The percentage of naive resting T cells (CD45RA) increased slightly (up to 8%, P < 0.05) whereas the percentages of memory T cells (CD45RO), T cells with IL-2 receptor (CD25), and natural killer cells (CD16) remained unaltered. The percentage of HLA-DR positive lymphocytes increased during CPB (up to 18%, P < 0.05), but it was decreased thereafter (up to 16%, P < 0.05). The percentage of monocytes (CD14) decreased first during CPB in both groups (up to 32%, P < 0.01), but it was higher in the autotransfusion device group (decreased 29% from initial value) than in the control group (decreased 65% from initial value) at the end of CPB (P < 0.05). This study shows that extracorporeal circulation has an effect on lymphocytes and their subset counts. The changes were slightly immunosuppressive. By contrast, use of autotransfusion devices had only minor effects.
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PMID:Effects of cardiopulmonary bypass on lymphocytes and their subset counts with or without use of autotransfusion devices. 780 41

Immunohistochemical and immunoserological evidence supports the involvement of both cell-mediated and humoral mechanisms in the pathogenesis of melanocyte destruction in vitiligo. Punch biopsies from depigmented vitiliginous skin (VS), normal-looking pigmented skin (PS), and marginal skin (MS) from patients with generalized vitiligo (n = 15) were labeled with K 1.2.58, OKM1 (CD11b), Leu 11b (CD16), Leu 19 (CD56), IFN-gamma receptor, IL-2 receptor (CD25), IgG, IgM, C3c, and C3d MoAbs. In addition, in vitro effects of vitiligo sera (n = 13) on human newborn melanocytes (HMel) under different culture conditions were studied. The immunohistochemical findings showed absence of K 1.2.58+ epidermal melanocytes in VS and abnormal morphology in MS. In these areas, a few CD11b+ cells in the dermis and epidermis could be detected but no significant numbers of CD16+ or CD56+ cells were seen among the mononuclear cellular infiltrate. IL-2 and IFN-gamma receptors were clearly expressed by the cellular infiltrate. No significant deposition of complement or immunoglobulin was seen. The addition of vitiligo sera to HMel cultures induced a significant cellular proliferation. The stimulation of cell proliferation occurred regardless whether the sera were added alone or when preheated (56 degrees C for 1 hr) and then supplemented with a complement source (P < 0.01 at 2%, P < 0.001 at 10%, and P < 0.01 at 20% for sera alone) (P > 0.05 at 2%, P < 0.05 at 10%, and P < 0.01 at 20% for decomplemented sera plus complement).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Further evidence for involvement of both cell mediated and humoral immunity in generalized vitiligo. 807 43

We evaluated adoptive immunotherapy using LAK cells combined with systemic administration of interleukin-2 (IL-2) in 11 patients with metastatic renal cell carcinoma. The LAK cells were generated by incubation in serum-free medium (AIM-V) supplemented with IL-2 (1,000 U/ml) for 4 days and were generally administered twice weekly (4 times/cycle). Daily administration of IL-2 (50 x 10(5) U) was started 3 days prior to the first LAK infusion and continued throughout the cycle. Each course of therapy comprised 1-6 cycles, with the total dose of LAK cells and IL-2 varying from 3.3-52.6 x 10(9) cells and 140-900 x 10(5) U, respectively. Clinical response was evaluated in terms of metastasis to specific organs (lung only: eight cases, lung and brain: one, lung and lymph nodes: one, lung and bone and pleuropericardium: one). The outcome was complete response in one patient, partial response in one, no change in six and disease progression in three. The response rate was 18.8%. This therapy was most effective against pulmonary metastases. Adverse reactions to LAK cell infusion included fever, headache, and chills. Eosinophilia and weight gain due to IL-2 administration were also observed. However, all of these symptoms were transient and no serious side effects occurred. In these patients, the proportion of natural killer (NK) cells (CD16) and cells with IL-2 receptor (CD25) among PBL was increased markedly in the early phase of therapy, and activated T cell (CD3+DR+) and suppressor T cells (CD8+11+) increased significantly at a later phase. It was suggested that the clinical response would be expected in case of increasing of CD16 cells or CD25 cells and augmentation of NK or LAK activity. Our results indicate that this regimen of adoptive immunotherapy shows some promise for the treatment of advanced renal cell carcinoma.
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PMID:[Study of adoptive immunotherapy for metastatic renal cell carcinoma with lymphokine-activated killer (LAK) cells and interleukin-2. II. Clinical evaluation]. 832 Aug 88

Interleukin 2 (IL-2) and interferon-alpha (IFN-alpha) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase 1B trial of IL-2 plus or minus IFN-alpha in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-alpha and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-alpha and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (1.5 x 10(6) units/m2/day or 3.0 x 10(6) units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-alpha (0.5 x 10(6) or 5 x 10(6) units/m2/day) was administered s.c. on days 1-4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/IFN-alpha for course 2, or IL-2/IFN-alpha in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2. A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-alpha. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-alpha. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-alpha group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum beta 2-microglobulin expression and indoleamine 2,3-dioxygenase activity. However, increases were not significantly different between patients receiving IL-2 alone and IL-2 plus IFN-alpha. No dose response effect for IFN-alpha was observed for any of the parameters assessed. Toxicities consisted primarily of constitutional toxicities, including fever, rigors, malaise, headache, anorexia, and a decrease in performance status. No clinically significant differences in toxicities were observed between courses consisting of IL-2 and those consisting of IFN-alpha and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A direct comparison of immunological and clinical effects of interleukin 2 with and without interferon-alpha in humans. 844 8


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