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)

We recently reported that the myristoylated peptide N-myristoyl-Lys-Arg-Thr-Leu-Arg (N-m-KRTLR) is a novel protein kinase C inhibitor. In this study, we investigated the biological effects of N-m-KRTLR using as an in vitro model the induction of the IL-2 receptor and IL-2 secretion by Jurkat cells in response to stimulation with 12-O tetradecanoylphorbol-13-acetate (TPA) plus phytohemagglutinin (PHA) and TPA plus OKT3 mAb. N-m-KRTLR significantly suppressed induction of the IL-2 receptor on the surface of the Jurkat cells by TPA plus either PHA or OKT3 mAb. Furthermore, N-m-KRTLR inhibited the production and release of IL-2 from cultured Jurkat cells stimulated with TPA plus either PHA or OKT3 mAb. Similarly, this peptide significantly inhibited the IL-2 production in normal human peripheral blood mononuclear cells in response to stimulation by TPA and PHA. In contrast, this peptide did not affect expression of the CD3 complex on the surface of the Jurkat cells either alone or in the presence of TPA or PHA. Furthermore, N-m-KRTLR did not interfere with the spontaneous proliferation of the Jurkat cells, and its effects on IL-2 secretion and IL-2 receptor expression in the Jurkat cells were evident without loss of cell viability. These results suggest that the novel protein kinase C inhibitor N-m-KRTLR may selectively inhibit certain activation pathways of Jurkat cells and indicate the usefulness of N-m-KRTLR in the analysis of discrete events in T cell activation.
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PMID:Inhibition of IL-2 receptor induction and IL-2 production in the human leukemic cell line Jurkat by a novel peptide inhibitor of protein kinase C. 212 73

Immunohistochemical study with various monoclonal antibodies to the mononuclear cell surface antigens was carried out on the regional lymph nodes in patients with cervical cancer to assess the augmentative effect of lentinan. Zero, 2, 4, or 6 mg of lentinan was administered i.v. one day prior to surgery to patients with cervical cancer (14 cases with FIGO stage 0 and 19 with FIGO stage Ib) and those with benign gynecologic tumors (8 cases with myoma uteri and 6 with ovarian tumor). Frozen sections of fresh pelvic lymph nodes obtained from these patients during surgery were stained by the ABC (avidin-biotin-peroxidase complex) method using several monoclonal antibodies to define the surface phenotype of mononuclear cells. The results were as follows: 1. Pelvic lymph nodes in patients with benign disease: In the absence of lentinan, lymphocytes stained with Leu 3a antibody were more numerous than those stained with Leu 2a, and both were observed mainly in the paracortical area (PC). The number of lymphocytes stained with Leu 4 antibody was practically equal to the sum of those stained with Leu 3a and Leu 2a. HLA-Dr positive lymphocytes were present in moderate numbers in PC and sinus. The above findings were not changed by the administration of lentinan. Cells stained with monoclonal antibodies including Leu 7, 11, M3, and IL-2 receptor (IL-2R) were very few or absent. 2. Pelvic lymph nodes in patients with cervical cancer receiving no lentinan: The findings obtained in these cases were much the same as those in patients with benign tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Antigenic phenotype of the lymphocytic component of regional lymph nodes in patients with cervical cancer and its modulation by lentinan]. 213 55

Recent data from studies of experimental murine tumors and certain human tumors (primarily melanoma) suggest that tumor-infiltrating T-lymphocytes (T-cell TILs) represent a highly potent and specific host antitumor response. We conducted an immunohistochemical analysis of the T-cell TIL subpopulations in frozen tissue sections taken from 82 consecutive B-cell diffuse large cell lymphoma (DLCL) patients. Initially, we analyzed the relationship in these patients between relapse-free survival (RFS) and their T-cell TIL characteristics. Nineteen patients had a low percentage (less than 6% of Leu-2+ (suppressor/cytotoxic) T-cell TILs, and 63 patients had a high percentage (greater than 6%) of Leu-2+ TILs. We found that a low percentage of Leu-2+ TILs correlated with a reduction in RFS: at 20 mo follow-up, all 19 low Leu-2+ patients had relapsed, whereas 70% of the 63 high Leu-2+ patients remained relapse-free (P = 0.008). No significant correlations appeared between patients' T-cell TIL subsets and overall survival. The percentage of newly diagnosed tumors with low counts of Leu-4+ (pan-T) TILs was marginally greater among interleukin-2 (IL-2) receptor-positive tumors than among IL-2 receptor-negative tumors (50 versus 28%, P = 0.098), which suggests that specific phenotypic characteristics of B-cell DLCL may modulate the host T-cell TIL response. Our results indicate that the host's T-cell TIL response in B-cell DLCL can be quantitated from frozen tissue sections and that this response may be related to disease course. Further related TIL studies may lead to new immunorestorative therapeutic approaches for patients with deficient or aberrant cytotoxic T-lymphocyte host responses.
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PMID:Tumor-infiltrating T-lymphocytes in B-cell diffuse large cell lymphoma related to disease course. 219 16

The interleukin-2 diphtheria toxin-related fusion protein (IL-2 toxin) inhibits protein and DNA synthesis IN rIL-2 (10(-10) M) stimulated T lymphoblasts in a dose-dependent fashion. However, prior to target cell death very low concentrations of rIL-2 and IL-2 toxin synergistically stimulate [3H] thymidine incorporation despite inhibition of [14C] leucine uptake. A sequential analysis of [3H] thymidine incorporation shows that high IL-2 toxin concentration (10(-9)-10(-7) M) stimulates DNA synthesis at 18 hr of culture and inhibits [3H] thymidine uptake after 24 hr, while low concentrations of IL-2 toxin (10(-12)-10(-10) M) exhibits stimulatory effects only after 24 hr of culture. Anti-Tac a monoclonal antibody directed against the p55 chain of the high affinity IL-2 receptor (IL-2R) blocks the stimulatory effects of high-dose IL-2 toxin, thereby proving that these effects are mediated through the IL-2 domain of the fusion protein. At 7 hr following interaction with IL-2R receptor (IL-2R)+ T cells, IL-2 toxin-treated cells evidence augmented transcription of the heat shock protein gene, an effect indistinguishable from those mediated by rIL-2. We conclude that interaction of IL-2 toxin with IL-2R+ T cells initially mimicks the stimulatory effects of IL-2 upon gene transcription and DNA synthesis yet concomitant inhibition of protein synthesis is evident.
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PMID:A kinetic analysis of the effects of interleukin-2 diphtheria toxin fusion protein upon activated T cells. 230 Oct 12

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

In this study we analyzed the ability of peripheral blood mononuclear cells (PBMC) from hemophilic patients (He) with negative or positive serology for the human immunodeficiency virus (HIV), to increase natural killer (NK) cytotoxicity upon stimulation with physiological and non physiological agents. Purified interleukin-2 (IL-2), the interferon (IFN)-inducer polyinosinic polycytidylic acid (PIC), recombinant alpha- and gamma-IFN and the protein kinase activator phorbol myristate acetate (PMA) were used as stimulatory agents. The NK functional response was correlated with the presence of PBMC bearing phenotypic markers of activated cells (IL-2 receptor, IL-2R) and of different NK cell maturation stages. Our results demonstrate that NK effector cells with slight lytic activity (Leu 7+ CD16-) predominated in HIV+ He patients. On the other hand the occurrence of IL-2R positive cells was similarly high in both HIV+ and HIV- individuals and was probably more related to chronic replacement treatment with Factor VIII or Factor IX concentrates than to HIV infection. The ability to respond to physiological NK regulators such as IL-2 and IFNs, or to the IFN-inducer PIC was impaired in HIV+ He, especially in HIV+ LAS individuals, suggesting that the inability of these cells to increase NK cell activity after appropriate induction was due to an intrinsic defect. Since phosphoinositide turnover and subsequent protein kinase C activation are thought to be part of the physiological mechanism of NK cytotoxicity, we studied the effect of PMA on PBMC from each group of patients. The ability to respond to PMA was lost only in PBMC from HIV+ LAS patients, indicating that impairment of the NK lytic mechanism progresses as the disease gets worse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV infection and natural killer cytotoxicity in hemophilic patients. 238 63

A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.
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PMID:Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). 241 63

The present study was performed to localize in the IL-2 molecule the active site responsible for interaction with the IL-2 receptor. To predict the receptor binding site on the IL-2 molecule, a computer programme based on the hypothesis that the active site will contain parts of the protein molecule having a high tendency to form a bend was utilized. The tendency to form a bend was evaluated by assessing the probability of beta-turn occurrence; the highest probability was found in the tetrapeptide Asn-Pro-Lys-Leu, occupying the positions 33-36 of the IL-2 molecule. Accordingly, the hexadecapeptide H-Cys-Nle-Gly-Ile-Asn-Asn-Tyr-Lys-Asn-Pro-Lys-Leu-Thr-Arg-Met-Leu-NH2 that spans over the predicted tetrapeptide Asn-Pro-Lys-Leu and comprises the region 27-40 from the IL-2 amino acid sequence was synthesized. This synthetic (I-16) peptide was found to selectively inhibit the IL-2-dependent uptake of 3H-TDR by CTLL cells, apparently by competing with IL-2 for the IL-2 receptor. The synthetic I-16 hexadecapeptide was conjugated to carrier (BSA) protein and used for immunization of rabbits. Resulting I-16 antibodies were capable of binding specifically to the I-16 hexadecapeptide in indirect ELISA test; they reacted substantially with IL-2-producing but not with IL-2-non-producing Jurkat cells in indirect cell membrane immunofluorescence, and inhibited activation of killer spleen cells with human recombinant IL-2 as detected by 51Cr microcytotoxicity assay. Taken together, these results suggest that at least one of the receptor contact sites of the IL-2 is localized within the N-terminal part of the molecule in the region defined by amino acids 27-40 and coded for by the exon 1 and 2.
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PMID:Localization of a receptor binding site on the IL-2 molecule. 244 71

Peripheral blood leukocytes from 5 patients with Melkersson-Rosenthal syndrome (MRS) were characterized with an immunoenzymatic staining technique utilizing ten different mouse monoclonal antibodies to cell surface antigens. No gross abnormalities could be found in the various T and B cell subpopulations. However, the proportion of cells expressing the IL-2 receptor was slightly increased, indicating the occurrence of activated lymphocytes in the circulation. Furthermore, in all 5 patients a large proportion of a non-phagocytic, Leu-M1-expressing, granulocyte-like cells of low density was found, probably reflecting the presence of activated granulocytes in the blood in MRS patients. The findings suggest that activation of both the lymphocyte and the granulocyte systems may be of importance in the pathogenesis of MRS.
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PMID:Phenotypes of peripheral blood leukocytes in Melkersson-Rosenthal syndrome. 245 96

We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor-associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype control antibody. T-cell pellets were employed during incubation to facilitate interaction between T-cell LFA-3 and CD2. CD2 blockade caused a 66% to 79% inhibition of p55 expression after three to six days of culture with IL-2. Next we assessed the effect of CD2 blockade on IL-2. Next we assessed the effect of CD2 blockade on IL-2-induced inhibition of BFU-E in autologous cocultures containing CD3-triggered T cells. IL-2 caused a dose-dependent inhibition (52% to 92%) of BFU-E in the presence but not in the absence of CD3-triggered T cells. T-cell CD2 blockade prior to CD3 triggering caused a 65% to 87% abrogation of IL-2-induced inhibition of BFU-E at 10 to 10(2) U/mL IL-2. Preincubation of CD3-triggered T cells with isotype control antibody had no effect on IL-2-induced erythroid inhibition. Day 3 supernatants from CD3-triggered T cells or CD2-blocked, CD3-triggered T cells established in the presence of IL-2 were next assessed for modulation of BFU-E. CD3-triggered T-cell supernatants caused a 77% +/- 9% inhibition of BFU-E. Blockade of CD2 caused a 95% abrogation of T-cell-mediated BFU-E inhibition. In addition, CD2 blockade reduced interferon-gamma (IF gamma) release (84 to 128 U/mL) from CD3-triggered T cells by 81% at day 3 of culture. In control experiments, the addition of IF gamma-neutralizing monoclonal antibody to CD3-triggered T-cell supernatant established in the presence of IL-2 caused 75% abrogation of IL-2 inhibition of BFU-E. We conclude that blockade of the CD2 T-cell determinant induces down modulation of (a) T-cell p55 IL-2 receptor expression, (b) IL-2-induced inhibition of BFU-E, and (c) IL-2-induced marrow T-cell IF gamma release. These data suggest that the T-cell CD2 determinant can exert a regulatory effect on the control of erythropoiesis by the lymphokine cascade.
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PMID:The T-cell CD2 determinant mediates inhibition of erythropoiesis by the lymphokine cascade. 245


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