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 56-year-old man with refractory B-cell lymphocytic non-Hodgkin's lymphoma was treated in a Phase II study with interleukin-2 (IL-2) (Roussel-Uclaf, Romainville, France). The patient had involvement of multiple lymph nodes and medullary and peripheral blood (3.6 x 10(9) monoclonal CD19-positive [CD19+] B-lymphocytes/l). After a 5-day cycle of IL-2 treatment, an eightfold increase of the monoclonal CD19+ population was observed (27 x 10(9) monoclonal CD19+ cells). The lymphocytosis decreased dramatically during the second cycle (days 15 to 19) of IL-2 treatment, resulting in 6 x 10(9)/l peripheral lymphocytes, with 5.5 x 10(9) B-lymphocytes. As soon as day 20, peripheral B-cells again increased considerably, with 32 x 10(9) CD19+ cells/l at day 27. The CD19+ population remained monoclonal as assessed by kappa/lambda cell-surface phenotyping and kappa gene rearrangement evaluation. Kinetics of the monoclonal B-lymphocyte response to IL-2 paralleled the natural killer/lymphokine-activated killer and T-cell response, with a 4-day latency period, suggesting an indirect enhancing effect of IL-2. Before and during IL-2 treatment, peripheral B-lymphocytes never expressed detectable levels of the p55 IL-2 receptor. However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population. Tumor necrosis factor alpha, a known (in vitro) B-cell tumor growth factor, reached high serum levels during IL-2 treatment. Response evaluation at day 45 showed stability of the lymph node involvement and the marrow lymphocyte infiltrate. At day 45, peripheral B-cell lymphocytosis was 7.5 x 10(9)/l. To the knowledge of the authors, this is the first report of an in vivo IL-2-induced reversible increase of peripheral monoclonal B-cell lymphocytosis.
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PMID:Interleukin-2-induced increase of a monoclonal B-cell lymphocytosis. A novel in vivo interleukin-2 effect? 156 83

Pulmonary involvement has been demonstrated in patients with spastic myelopathy associated with HTLV-I infection (HAM/TSP). Pulmonary lesions in these patients are characterized by T-lymphocytosis and increased level of soluble IL-2 receptor in bronchoalveolar lavage fluid. T-lymphocytes from peripheral blood and bronchoalveolar lavage fluid proliferated spontaneously and released IL-2 and IL-2 receptor when cultured in vitro. Spontaneous proliferation of T-lymphocytes was also found in HTLV-I carriers without myelopathy, but less intensely than in HAM/TSP patients. Interestingly, HTLV-I-infected cells were markedly increased in bronchoalveolar lavage fluid from HAM/TSP patients compared to HTLV-I carriers without myelopathy. These results suggest that T-lymphocyte activation and increased HTLV-I-infected cells play an important role in the pathogenesis of pulmonary involvement in patients with HAM/TSP.
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PMID:[Pathogenesis of T-lymphocyte alveolitis associated with HTLV-I infection]. 163 41

The lymphocytosis manifested in infectious mononucleosis (IM) during acute phase is ascribed to a reactive expansion of CD8+ T lymphocytes caused by Epstein-Barr virus (EBV)-infected B lymphocytes. Expression of HLA-DR antigen on IM lymphocytes suggests that these T lymphocytes are somehow activated in vivo. In the present study, we analyzed the interleukin-2 (IL-2) receptor expression on lymphocytes from six patients with acute IM. Radiolabeled IL-2 binding assay revealed that IM lymphocytes from all patients examined had a considerable number of IL-2 binding sites with an intermediate affinity, although they did not express the IL-2 receptor recognized by anti-Tac antibody (p55). The number of binding sites (1,070 to 4,600 sites per cell) was larger than that of a normal, resting T lymphocyte-enriched population (650 sites per cell). Furthermore, IM lymphocytes showed marked proliferative responses to higher concentrations of IL-2, which were almost completely blocked by an anti-p70 IL-2 receptor antibody, indicating that their IL-2 receptor is a functional receptor. The results of an affinity cross-linking study seem to indicate that the IL-2 receptor expressed on IM lymphocytes is p70, the second chain of the IL-2 receptor distinct from p55. Flow cytometric analysis following immunofluorescent staining with anti-p70 IL-2 receptor antibody confirmed p70 expression on CD8+ HLA-DR+ lymphocytes. These data suggest that p70 IL-2 receptor expression is involved in the immune response triggered by EBV infection.
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PMID:Selective expression of the p70 subunit of the interleukin-2 receptor on lymphocytes from patients with infectious mononucleosis. 229

Patients with HTLV-I-associated myelopathy (HAM) show subclinical pulmonary involvement. Bronchoalveolar lavage (BAL) studies of HAM patients have shown that there is T-lymphocytosis in association with increased soluble IL-2 receptor levels in BAL fluid. Furthermore, BAL lymphocytes as well as peripheral blood lymphocytes obtained from HAM patients proliferated spontaneously when cultured in vitro. The lymphocytes proliferating were T-lymphocytes (both CD4+ cells and CD8+ cells) and released soluble IL-2 receptors in supernatant fluid. These results indicated that T-lymphocytes were activated in HAM patients. In conclusion, activated T-lymphocytes may play an important role in the development of the spinal cord and pulmonary lesions in HAM patients.
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PMID:[Pulmonary involvement in HTLV-I-associated myelopathy]. 233 48

Lymphocytes, co-expressing CD4/Leu7 and CD8/Leu7 markers respectively, taken from two patients having large granular lymphocytosis taking an indolent clinical course have been comparatively studied for function as NK cells and T cells. Both large granular lymphocytes (LGLs) were acid phosphatase positive and showed a beta-glucuronidase reaction in their cytoplasmic granules. Studies on case 1 indicated that the CD4/Leu7 lymphocytosis with LGL morphology takes a benign clinical course with mild neutropenia as well as those of CD8/Leu7 LG lymphocytosis. Both CD4/Leu7 and CD8/Leu7 LGLs behave similarly in their lack of NK activity, and manifest decreased IL-2 production in vitro and show a low IL-2 receptor expression unrelated to their T cell phenotype, but behave differently in influencing the immunoglobulin production in vitro and the ADCC activity, depending on their T cell phenotype and on the expression of Fc receptor, respectively. Furthermore, the altered Fc receptors which were undetectable by the Leul 1 antibody but were still effective for ADCC activity might be present in case 2 LGLs.
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PMID:CD4/Leu7 and CD8/Leu7 large granular lymphocytosis: comparative studies between NK cells and T cells. 251 16

The surface marker phenotype of lymphocytes derived from 12 patients with B-CLL was compared to that of lymphocytes from 10 patients with an other monoclonal but clinical benign form of B-cell proliferative disorder termed monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS). A panel of well characterized monoclonal antibodies was used for the surface marker determinations. The mean total number of B cells (CD20) was 8.5 x 10(9)/1 in B-MLUS as compared to 44 x 10(9)/1 in B-CLL (p less than 0.001). B-CLL had a greater imbalance in T-cell subpopulations than B-MLUS and healthy controls. Total numbers of CD3+, CD8+ cells as well as cells expressing the NK-related antigens (CD16, Leu-7) and IL-2 receptor (CD25) bearing lymphocytes were statistically significant higher in B-CLL than in B-MLUS. Analyses of B-cell enriched populations showed that B-CLL represented B cells of an early maturation stage, whereas B cells from B-MLUS were more mature as judged by the loss of the CD21 surface marker. A larger fraction of B cells in B-CLL compared to B-MLUS exhibited a higher activation stage as revealed by the expression of the CD21, CD25 and CD35 structures as well as the FMC7 antigen.
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PMID:Higher T-cell imbalance and growth factor receptor expression in B-cell chronic lymphocytic leukemia (B-CLL) as compared to monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS). 2831 41

The adoptive immunotherapy of human cancer using lymphokine-activated killer (LAK) cells in combination with high-dose systemic recombinant interleukin-2 (rIL-2) has been associated with global changes in several hematological and immunological parameters while imposing profound toxicity on patients. We have evaluated an alternative LAK cell therapy utilizing low-dose systemic rIL-2 is also characterized by significant changes in immunological and hematological parameters, which are qualitatively similar to those induced by high-dose rIL-2. Low-dose systemic rIL-2, given by i.v. bolus, is cleared to baseline levels within 240 min of administration. The induction of lymphocytosis and eosinophilia, which has characterized other protocols, is also a feature of this protocol. In addition, low-dose systemic rIL-2/LAK cell immunotherapy results in increased peripheral blood mononuclear cell (PBMC) expression of T-cell activation markers such as OKIa, OKT10 and IL-2 receptor. PBMC sampled approximately 100 h after the final infusion of LAK cells demonstrated a statistically significant increase in their ability to kill natural killer (NK)-sensitive and NK-resistant cell lines such as K562 and Daudi compared to baseline values (P less than .05). These data suggest that rIL-2-based immunotherapy using low-dose rIL-2 is capable of inducing quantitative hematological and immunological changes while (in combination with LAK cells) retaining the ability to mediate tumor regression in vivo.
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PMID:Immunomodulatory effects of systemic low-dose recombinant interleukin-2 and lymphokine-activated killer cells in humans. 259 83

It has been shown that there are pulmonary involvements in patients with HTLV-1-associated myelopathy (HAM). Pulmonary lesions found in HAM are characterized by T-lymphocytosis and increased levels of soluble IL-2 receptor in bronchoalveolar lavage fluid. Peripheral blood lymphocytes from HAM patients proliferated spontaneously when cultured in vitro. Lymphocytes proliferated were positive for CD3 and HLA-DR staining. There were CD4+ cells and CD8+ cells in proliferating T-lymphocytes 5 days after cultivation. Culture supernatants of proliferating cells showed an increased soluble IL-2 receptor. These results suggest that activated T-cells play an important role in developing pulmonary lesions in HAM.
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PMID:[Pathogenesis of pulmonary involvement in HTLV-I-associated myelopathy (HAM): studies on T-cell function]. 261 72

The purpose of this study was to compare the toxicity, immunomodulatory changes, and antitumor efficacy of interleukin 2 (IL-2) and lymphokine activated killer (LAK) cell therapy with two durations of IL-2 infusion. Patients with progressive melanoma, non-Hodgkin's lymphoma, renal carcinoma, or colon carcinoma received IL-2 at 3 X 10(6) units/m2/day on days 1-5 and 13-17, either by bolus injection every 8 h (q8h) or by continuous i.v. (CIV) administration. Peripheral blood mononuclear cells were harvested by leukapheresis on days 8, 9, and 10, were incubated in vitro for 5 days for generation of LAK cells, and were infused on days 13, 14, and 15. The first 11 patients were treated with IL-2 q8h, and the subsequent 13 patients were treated by CIV infusion. Toxicity consisted primarily of fever, chills, emesis, diarrhea, weight gain, and edema but did not require intensive care unit support and did not differ significantly between treatment groups. IL-2-induced lymphocytosis on day 8 was higher with CIV than with q8h administration with a mean lymphocyte count/microliter of 5610 +/- 700 (SE) versus 3300 +/- 500. Immunomodulatory changes observed on days 8 and 20 were also greater with CIV IL-2 and included an increase in peripheral blood mononuclear cell IL-2 receptor expression as well as a marked rise in the number of Leu-11+ and Leu-19+ peripheral blood mononuclear cells. The total leukapheresis yield per patient and total number of LAK cells infused per patient were higher with CIV than q8h administration, with 49.8 +/- 4.9 X 10(9) versus 39.4 +/- 5.4 X 10(9) and 42.6 +/- 5.0 X 10(9) versus 34.0 +/- 5.4 X 10(9), respectively. The cells infused displayed phenotypic evidence of activation and exhibited marked lytic reactivity to Daudi, Raji, and HT-144 targets. One complete and one minimal response were observed in 2 of 8 patients with metastatic renal cell carcinoma who received CIV IL-2 and LAK cells. The results show that IL-2 is more biologically active by CIV than q8h administration, as demonstrated by greater rebound lymphocytosis, LAK cell yield, and in vivo immunostimulation.
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PMID:Influence of schedule of interleukin 2 administration on therapy with interleukin 2 and lymphokine activated killer cells. 278 43

Expression of the low-affinity interleukin-2 (IL-2) receptor molecule (TAC) has been associated with lymphocyte activation, in vitro and in vivo [Greene WC (1987) Clin Res 35:439]. We have used an enzyme-linked immunosorbent assay (ELISA) to quantify the role of released and cell-bound IL-2 receptor following in vitro or in vivo activation of human lymphocytes with IL-2. In vitro experiments, culturing fresh peripheral blood lymphocytes in 30 U/ml IL-2 (corresponding to the steady-state IL-2 concentration achieved in patients receiving IL-2 in our clinical trials), showed that the levels of IL-2 receptor released into the culture media exceeded the levels of cell-associated receptor, with both rising in parallel to the cytotoxic activity of the peripheral blood lymphocytes (PBL) against cultured tumor cells. In 12 patients receiving high-dose IL-2 for the treatment of various malignant neoplasms, the levels of IL-2 receptor released into the serum rose dramatically during the IL-2 infusion, and then fell following cessation of the IL-2 infusion. This heightened release of IL-2 receptor into the serum occurred during the episodes of profound lymphopenia that developed within hours after patients began an IL-2 infusion. Following each 4-day infusion of IL-2, a rebound lymphocytosis was observed, as has been previously reported. Serum IL-2 receptor levels do not rebound in parallel; rather, they reach a plateau near the end of the 4-day infusion and then decrease upon cessation of IL-2. These changes in serum IL-2 receptor levels accompany changes in lytic activity of circulating PBL on Daudi target cells. These results suggest that lymphocyte populations exposed to IL-2 in vivo are activated to become cytotoxic, release TAC, and relocate in non-peripheral blood compartments. Following cessation of the IL-2 infusion these activated lymphocytes return to the peripheral circulation and do not secrete TAC as vigorously as while influenced directly by the IL-2 infusion.
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PMID:Serum levels of the low-affinity interleukin-2 receptor molecule (TAC) during IL-2 therapy reflect systemic lymphoid mass activation. 278 94


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