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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 natural-killer(NK)-cell-mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of cocultures of spleen cells with OK432 contained interleukin-2 (IL-2) and interferon (IFN), mainly IFN-gamma. As the anti-(mouse IFN-gamma) monoclonal antibody but not anti-(mouse IFN-alpha) antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The enhancement of NK cell activity and production of IL-2 were partially inhibited by the pretreatment of spleen cells with mitomycin C or irradiation, and were completely abolished by pretreatment with actinomycin D. The IL-2 activity after treatment with various metabolic inhibitors ran parallel to the NK activity in a system augmented with OK432. The activity of incubated spleen cells with IL-2 receptors was increased by OK432 treatment, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-(mouse IL-2 receptor) monoclonal antibody, to block the interaction between IL-2 and these receptors of effector cells. The panning method clarified that the incubated spleen cells with IL-2 receptors are responsible for the production of IFN-gamma. These results suggest that IL-2 plays a major role in inducing the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.
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PMID:Role of interleukin-2 and interferon-gamma in induction of activated natural killer cells from mice primed in vivo and subsequently challenged in vitro with the streptococcal preparation OK432. 249 80

We have investigated the functional ability of a choriocarcinoma-cell-derived factor to block human T cell responses and the factor's immunoregulatory site of action on the T cell signal transduction pathway. The factor completely suppressed human T cell responses activated by phorbol ester and calcium ionophore, reagents which strongly stimulate IL-2-mediated T cell responses. It failed to inhibit CD 25 expression and IL-2 production by T cell blasts in the T cell activation phase, but completely blocked recombinant IL-2-induced proliferation of T cell blasts in the T cell proliferation phase. Absorption experiments with the factor and Con A-induced T cell blasts as well as [125I]IL-2 binding experiments with T cell blasts revealed that the factor acted on the physiological events occurring after IL-2-mediated stimulation of IL-2 receptor complexes, demonstrating no interaction of the factor with either IL-2 molecules or IL-2 receptor complexes. Moreover, it suppressed murine IL-2 dependent T cell line proliferation, suggesting the presence of common pathways in human and murine T cell proliferation. The biological and immunological significance of the factor during pregnancy and in the immunosuppressed tumor-bearing hosts are discussed.
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PMID:Analysis of site of action of a choriocarcinoma-derived immunoregulatory factor on IL-2-mediated T cell responses. 250 14

We examined the nature of cytoplasmic signal transduction pathways in cord blood T cells by stimulating them with tumor promoter (TPA) and calcium ionophore (A23187). Costimulation of T cells with TPA and A23187 induced optimal proliferative responses on Day 2 in cord T cells but on Day 4 in adult T cells. The maximal responses observed in cord T cells were much less than those of adult T cells, whereas the Con A-induced proliferative responses of these cells showed no significant differences. The reduced responses of cord T cells were due to their lower efficiency in activating the cellular events in T cell activation and proliferation phase, because cord T cells have significantly less ability than adult T cells to express IL-2 receptor as well as HLA-DR and produce IL-2 molecules, thereby inducing proliferation. These data show immature characteristics of intracellular signal transduction pathways in cord T cells, which are directly related with the functional immaturity of cord T cells.
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PMID:Demonstration of functional immaturity of signal transduction pathways in human cord T cells. 251 Sep 37

The natural killer (NK) cell mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of coculture of spleen cells with OK432 contained Interleukin 2 (IL-2) and Interferon (IFN), mainly IFN-gamma. As the anti-mouse IFN-gamma monoclonal antibody but not anti-mouse IFN-alpha antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The incubated spleen cells with IL-2 receptors increased with OK432 treatment by flow cytometry, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-mouse IL-2 receptor monoclonal antibody to block the interaction between IL-2 and these receptors of effector cells. By panning method, it was clarified that the incubated spleen cells with IL-2 receptors were responsible for the production of IFN-r. These results suggest that IL-2 plays a major role to induce the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.
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PMID:[Role of interleukin 2 and interferon gamma in induction of activated natural killer cells by the streptococcal preparation OK432]. 251 33

The current interest in adoptive immunotherapy of cancer has stimulated research into novel approaches of activating lymphocytes in vitro. We have studied the effect of anti-CD3 antibody on the in vitro activation of peripheral blood lymphocytes and tumor infiltrating lymphocytes (TIL) taken from patients with nonsmall cell cancer of the lung (NSCC). We demonstrate that anti-CD3 substantially enhances the proliferative response and bulk culture growth of interleukin 2 (IL-2)-activated killer cells. The addition of anti-CD3 to IL-2-treated TIL enhances their cytotoxicity against fresh autologous NSCC tumor targets, but not against the cancer cell lines K562 and M14. The effectors generated by culture in IL-2 and anti-CD3 have greatly increased IL-2 receptor expression and are predominantly CD4+ cells. These results establish anti-CD3 as a potentially powerful agent in the in vitro activation of lymphocytes from cancer patients.
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PMID:In vitro activation of lymphocytes from nonsmall cell cancer patients by interleukin 2 and anti-CD3 antibody. 253 64

Eight T lymphoblastoid cell lines transformed by Herpesvirus saimiri were studied for requirement of interleukin 2 (IL-2) for growth in tissue culture and expression of the IL-2 receptor. The results show that four cell lines grew independent of IL-2, but four other cell lines required IL-2 for optimal growth. However, all H. saimiri transformed cells expressed IL-2 receptors, regardless of IL-2 requirement. Between 2,250 and 8,800 high-affinity receptor sites/cell were detected by ligand-binding assays; in contrast, only about 1,000 sites/cell were in an uninfected IL-2-dependent marmoset T cell line. Surface-bound IL-2 was internalized and antibodies to the receptor inhibited cell growth. Expression of IL-2 receptors may allow expansion of tumor cells in vivo in response to endogenous or exogenous IL-2.
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PMID:Expression of interleukin 2 receptors in T cells transformed by strains of Herpesvirus saimiri representing three DNA subgroups. 255 Mar 88

Tumor-infiltrating lymphocytes (TILs) are often seen in non-small cell lung cancers (NSCCs). Their functional role in the pathogenesis of lung cancer is unknown. The authors studied TILs in 27 patients with NSCC and determined the following: (1) the immunologic phenotype as defined by monoclonal antibodies against various surface markers, (2) activation state as indicated by interleukin-2 (IL-2) receptor expression and the kinetics of proliferation response to IL-2, and (3) the ability to develop lymphokine-activated killer (LAK) type cytotoxicity against both natural killer (NK)-resistant tumor cell targets (M14) and fresh autologous tumor cells. The authors' results show TILs from NSCCs to be a heterogeneous population composed of T-cells, B-cells, monocytes, and NK cells in frequencies similar to those found in peripheral blood lymphocytes (PBLs). TILs demonstrated increased IL-2 receptor expression and a more rapid proliferative response to IL-2 than PBLs, implying activation of TILs by the tumor milieu. Finally, TILs generated cytotoxicity against NK-sensitive (K562) and NK-resistant (M14) cell line targets consistently after in vitro treatment with IL-2 but were less consistent in their ability to lyse fresh autologous tumor cells and less effective than PBL LAK cells in lysing all targets. Comparison with LAK cells generated from normal volunteers suggests that decreased killing of autologous tumor cells only partially results from an inherent resistance to lysis by fresh NSCC targets. It appears, therefore, that tumor cells taken from NSCCs are not readily killed by the immune cells that infiltrate the tumor stroma and that this failure does not result from nonspecific immune deficiency in TILs.
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PMID:Lymphokine-activated killer (LAK) cell activity in tumor-infiltrating lymphocytes from non-small cell lung cancer. 255 92

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

Activated lymphocytes can release a soluble form of IL-2 receptor (sIL-2R), which retains the capacity to bind IL-2. Abnormally high values of sIL-2R have been observed in patients with advanced solid tumors. In an attempt to further understand the biological significance of sIL-2R in solid tumors, this study investigated the relation between sIL-2R and Tac-positive cells. sIL-2R serum levels and Tac-positive cells were determined in 18 patients with solid tumors metastatic, 108 non-metastatic. Tumor types were: breast 7; lung 6; colon 2; stomach 1; testis 1; larynx 1. No correlation was found between circulating sIL-2R values and Tac-positive cells, and there was no difference between Tac-positive cell mean number in patients with high and normal sIL-2R levels. These preliminary results suggest that different mechanisms are responsible for sIL-2R release in the blood and IL-2 receptor expression on the immune cell surface.
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PMID:Interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors in patients with solid tumors are not correlated. 261 85

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90


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