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 factor enhancing proliferation of human peripheral blood lymphocytes (PBL) was identified in the culture supernatant of a human myeloid cell line HL-60 after ion exchange separation. Partially purified lymphocyte growth enhancing factor (LGEF) was found to enhance mitogen-stimulated PBL or purified T cell proliferation in a dose dependent fashion. LGEF alone did not stimulate PBL or T cell proliferation and its activity was dependent on the presence of mitogen. LGEF mediated T cell proliferation was neither accompanied by an increase in the level of IL-2 receptor expression, nor was dependent on the presence of monocytes. In ELISA assay antibodies against IL-1, IL-2, IL-3 and IL-6 did not recognize the LGEF preparation. The comparison of LGEF with other lymphokines is discussed.
Cancer Lett 1991 Jan
PMID:Identification of a co-stimulatory factor for human T cell proliferation. 200 56

The IL-2/IL-2 receptor (IL-2R) system has been investigated in 64 patients with multiple myeloma (MM), 31 with monoclonal gammopathies of undetermined significance (MGUS) and 20 normal controls. The MM data were related to clinical status by comparing active disease, i.e. at diagnosis and at relapse, and stable disease, i.e. complete remission and off-treatment plateau phase. Serum and urinary values of the soluble IL-2R (sIL-2R) were significantly increased in MM patients compared with normal controls and this increase was related to activity. MM patients with active disease gave significantly higher values than those with stable disease. Compared with normal controls, enriched B cell (but not T cell) preparations from peripheral blood mononuclear cells (PBMC) showed significantly increased proportions of IL-2R+ cells in MM and MGUS. However, the highest proportions were detected in active MM compared with stable MM and MGUS. Also, 16% of all MM patients, as opposed to 9% of MGUS, had well-defined bone marrow IL-2R+ plasma cell populations. The lowest serum IL-2 values were found in active MM. Serial follow up of serum sIL-2R suggested that this peptide can be used as an additional marker of active malignancy. The data indicate that a disturbance of IL-2/IL-2R system is most pronounced in active MM. These findings may provide clues as to the T cell abnormalities in MM.
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PMID:A disturbance of the IL-2/IL-2 receptor system parallels the activity of multiple myeloma. 204 21

Cytotoxic T lymphocytes (CTL) are believed to play an important role in the regression of advanced malignancies in response to adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Because the current limitations to the use of adoptive immunotherapy are the IL-2 dose-dependent toxicities and the difficulty in expanding the effector cell population, recent investigations have focused on the development of newer methods for generating CTL in vitro. IL-1 and IL-6 have been shown to synergistically promote thymocyte proliferation; however, their effect on CTL development has not been studied. We investigated the ability of these two cytokines to induce CTL development from immature thymocytes. Thymocytes from 5-week-old BALB/c mice were cultured for 72 hours in the presence of Con A and recombinant IL-1, IL-6, or IL-1 plus IL-6. Cytotoxicity against 51Cr-labeled P815 target cells was then measured in the presence of submitogenic doses of PHA. Neither IL-1 nor IL-6 induced a significant number of CTL from immature thymocytes. However, these two cytokines synergistically induced maximal CTL development. The monoclonal antibody to IL-4 completely abrogated CTL development induced by IL-1 and IL-6, but antibody to the IL-2 receptor had no effect. The data suggest that IL-1 and IL-6 can provide an additional method for in vitro CTL generation in adoptive immunotherapy of advanced tumors.
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PMID:Induction of cytotoxic T lymphocyte development from murine thymocytes by IL-1 and IL-6. 205 98

We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro. 211 74

Synergistic effect of recombinant IFN-gamma (IFN-gamma) and OK-432, a streptococcal preparation, using chromium release assay was studied in vitro on killer cell induction. The target cells utilized for assay were a human leukemia cell line K562, a human renal carcinoma cell line KU-2, autologous normal kidney tissues and autologous renal cell carcinomas. Culture supernatant of peripheral blood lymphocytes (PBL) and OK-432 (designated as OK conditioned medium or OK-CM) demonstrated enhanced cytotoxicity of fresh PBL against these target cells. Killer cell activity against autologous cancer cells could be also induced from PBL of renal cell carcinoma patients. Pretreatment of PBL with IFN-gamma revealed synergistic effect of OK-CM on killer cell induction. OK-CM derived from patients was shown to contain IL-2 activity as well as high titer of interferon. Neutralizing monoclonal antibody against IFN-gamma and IL-2 receptor demonstrated reduction of cytotoxicity. These results suggested potential benefit of sequential use of IFN-gamma and OK-432 for the treatment of metastatic renal cell carcinoma.
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PMID:Combination therapy for renal cell carcinoma using IFN-gamma and OK-432: in vitro study. 211 48

Peripheral blood lymphocytes, regional lymph node lymphocytes or malignant effusion lymphocytes from cancer patients were incubated with crude IL-2 (cIL-2) for 13 days. These effectors, which frequently expressed IL-2 receptor (IL-2R), proliferated well and possessed augmented killing activity against fresh autologous tumor cells and K562. However, when recombinant IL-2 (rIL-2) was added for the last 4 days of culture instead of cIL-2, IL-2R expression and killing activity against fresh autologous tumor cells decreased significantly (P less than 0.05). Phenotypic analysis indicated that cIL-2 significantly promoted the expansion of the cytotoxic population (CD8+.11b-)(P less than 0.05). The decreases in killing activity and IL-2R expression were restored by 0.004% PHA plus rIL-2, but not in the presence of rIFN-gamma, rIL-1 alpha, rIL-1 beta, rIL-4 or rIL-6. PHA-free cIL-2 maintained killing activity, but not IL-2R expression. We conclude that some factors in cIL-2 and a low dose of PHA-P are necessary for the maintenance of killing activity and IL-2R expression of cultured lymphocytes in the late phase of culture.
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PMID:Comparison between crude interleukin-2 and recombinant interleukin-2 in maintaining killing activity of cultured lymphocytes. 211 1

Synergistic and cooperative effects in vitro of OKT3, interleukin 2 (IL-2), and tumor necrosis factor alpha (TNF) as stimuli in generating effectors with lymphokine-activated killer activity were studied. Activation of human peripheral blood mononuclear cells with OKT3 (10 ng/ml) for 48 h, followed by culture in low concentrations of IL-2 (10 units/ml) and TNF (250 units/ml) resulted in higher cell recovery (50- to 3300-fold) compared to the number of cells in the initial culture and enhanced lytic activity against both Raji and fresh lung tumor targets (mean 100-fold) by day 30 compared to those expanded with higher concentrations of IL-2 (100 units/ml) alone. Immunofluorescence analysis of peripheral blood mononuclear cells initiated with OKT3 and expanded with IL-2 plus TNF revealed a selective increase in CD8+ cells and a decrease in CD4+ by day 28; the opposite effect was observed when cells were incubated with 100 units/ml of IL-2 alone, resulting in a greater proportion of CD4+ cells. Almost all cells were CD3+. Studies of cytokine receptor expression indicated that OKT3 plus IL-2 plus TNF caused an earlier up-regulation of the IL-2 receptor beta chain (Tac) and higher TNF receptor expression by day 6 compared to 100 units/ml IL-2 alone. Significant TNF levels (greater than 17 units/ml) were measured in culture supernatants from peripheral blood mononuclear cells initiated with OKT3 alone. Collectively, our data demonstrate that induction of lymphokine-activated killer activity with OKT3, followed by culture in low concentrations of IL-2 plus TNF is an alternative to the use of high-dose IL-2 alone and suggest that this combination may provide potential advantages in long-term generation of cytolytic cells.
Cancer Res 1990 Jun 15
PMID:Characterization of OKT3-initiated lymphokine-activated effectors expanded with interleukin 2 and tumor necrosis factor alpha. 216 Mar 21

Simultaneous determination of blood/lung ADA activity and T-lymphocyte subsets was conducted in 12 patients with active pulmonary tuberculosis, 12 patients with bronchogenic carcinoma and 11 healthy volunteers. Differences were significant only in the tuberculosis patients, namely, increased mean enzyme values in both the peripheral blood (36.68 +/- 10.90 U/L) and in the BALF (4.25 +/- 2.19 U/L), and correlation of ADA activity between the blood and the diseased lung only; the difference in elevated enzymatic activity between the tuberculosis group and the cancer group was of no statistical significance. We conclude that simultaneous ADA analysis of the blood and the BALF may be of diagnostic value in cases suspected of having tuberculosis as yet undiagnosed by other means. Based on the lowest value of enzymatic activity in the blood of patients with tuberculosis (28 U/L), the test has a sensitivity of 75 per cent and a specificity of 100 per cent; whereas the lowest value in the BALF of tuberculosis patients (2.9 U/L), the test has a sensitivity of 77 per cent and a specificity of 82 per cent. Findings that there was a blood-lung correlation of elevated ADA activity and a correlation of enzymatic elevation with increased numbers of T-cells bearing IL-2 receptor in cases of pulmonary tuberculosis only provide evidence in support of T-lymphocytes actively participating in the ongoing immune process.
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PMID:The association of adenosine deaminase activity with T-lymphocytes and subsets in pulmonary tuberculosis and bronchogenic carcinoma. 221 11

Expression of IL-2 receptor and proliferative response to rIL-2 of PBMC were studied in 48 patients with malignant diseases and in 50 normal subjects. Having been activated by PHA, PBMC from cancer patients had about the same percentage of Tac positive cells as compared with the normal subjects. However, resting and Con A-activated PBMC showed a significantly weaker proliferative response to rIL-2 in cancer patients than in normal subjects (P less than 0.001-0.005). The decrease in PBMC proliferative response to rIL-2 in patients with malignant diseases might be due to a defect in the formation of high affinity IL-2 receptors.
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PMID:[Expression of interleukin 2(IL-2) receptor and proliferative response to rIL-2 of peripheral blood mononuclear cells (PBMC) in patients with malignant diseases]. 227 64

We describe a new, spontaneously occurring BALB/c-derived murine T-cell leukemia. The leukemic cells, designated LB, grow rapidly and progressively in the syngeneic host with no signs of effective immunological resistance. LB cells expressed the Thy-1+, Lyt-2+, L3T4-, CD3- class-I+, CD25+ (IL-2 receptor, IL-2R), class-II-, gp70- phenotype. As LB cells express IL-2, as indicated by staining with 2 distinct anti-CD25 IL-2R monoclonal antibodies (MAbs), the therapeutic efficacy of IL-2-diphtheria toxin-related protein was tested on this leukemic model. IL-2-diphtheria toxin, but not diphtheria toxin, efficiently inhibited the proliferation of LB cells. The proliferation of a murine myeloma cell line, which does not express IL-2R, was not inhibited by IL-2-diphtheria toxin. The possible implantation of this animal model in fundamental and practical studies is discussed.
Int J Cancer 1990 Jan 15
PMID:Murine spontaneous T-cell leukemia constitutively expressing IL-2 receptor--a model for human T-cell malignancies expressing IL-2 receptor. 229


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