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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor infiltrating (TIL) and peripheral blood lymphocytes (PBL) were isolated from 18 patients with non-small cell lung cancer undergoing radical surgery. Surface marker analysis revealed that TILs and PBLs mainly consisted of CD3+ T cells and that TILs generally displayed a lower CD4/CD8 ratio. Differences were found in the expression of CD25 (IL-2 receptor) and DR (MHC class II) antigens, which were increased in TILs, and in the percentage of CD16+ natural killer (NK) cells, which was reduced in TILs as compared to PBLs. Accordingly, the NK activity of TILs was lower than that of PBLs, whereas neither TILs nor PBLs expressed spontaneous cytolytic activity against fresh autologous tumor cells, melanoma cells and the "NK-resistant" A549 lung carcinoma cell line. After 4 days of culture in medium with recombinant-interleukin-2 (rIL-2), TILs and PBLs acquired cytolytic activity against all cell targets, but TILs expressed higher levels of cytotoxicity than autologous PBLs only in 3 patients out of 16 tested. More importantly, both TILs and PBLs displayed similar levels of cytotoxic activity against autologous tumor cells. TILs and PBLs from 8 patients were also analyzed by a limiting dilution microculture system. Cloning efficiency was remarkably lower in TILs, and surface marker analysis of T cell clones confirmed that an accumulation of CD8+ lymphocytes, which displayed cytolytic activity in a lectin-dependent assay, occurred at the tumor site. The non-MHC-restricted cytolytic activity of TIL- and PBL-derived T cell clones against K562, A549, and allogeneic melanoma cells and the cytolytic activity against autologous tumor cells showed no significant differences. Only 53% of TIL clones released IL-2 in response to PHA + TPA stimulation, whereas 68% of PBL-derived clones were IL-2 producers. Moreover, most PBL- and TIL-derived clones released tumor necrosis factor alpha in response to mitogen stimulation.
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PMID:Peripheral blood and tumor infiltrating lymphocytes in non-small cell lung cancer: analysis at the population and clonal level. 217 60

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

This paper examines the possibility of a functional linkage between class I MHC molecules and the T-cell receptor complex for antigen (T3-Ti). A newly developed anti-CD3 antibody (500A2) was used as an activation signal for EL4 lymphoma cells and allospecific cytotoxic T-cell clones (CTL), and the production of IL-2/IL-2 receptor in EL4 cells and serine esterase in CTL was determined. Anti-CD3 antibody-induced activation of both EL4 and CTL cells was enhanced in the presence of immunologically cross-linked and immobilized anti-H-2 (class I) antibody reactive against the H-2 haplotype of the responding T cells. A number of H-2-negative and H-2-positive EL4 subclones were generated and tested for anti-CD3 antibody-induced IL-2/IL-2 receptor production. Although both H-2-positive and -negative subclones expressed CD3 antigen and produced IL-2 after activation with the phorbol ester TPA, only the H-2-positive cell clones produced IL-2 and expressed IL-2 receptor after anti-CD3 antibody induction. Our results are compatible with the existence of a functional linkage between the class I and the CD3 molecules on the surface of T cells.
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PMID:T-cell activation. I. Evidence for a functional linkage between class I MHC antigens and the Tc-Ti complex. 252 6

Human T lymphocyte proliferation induced by neuraminidase-galactose oxidase (NAGO)-treated autologous erythrocytes (HENAGO) plus polyethylene glycol (PEG) has previously been shown to be independent of accessory cells. Here, we show that the response to HENAGO + PEG was accompanied by interleukin 2 (IL-2) release and was inhibited by anti-IL-2 and anti-IL-2 receptor antibodies. HENAGO alone initiated DNA synthesis together with phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate; TPA). To elucidate the nature of the stimulatory signals NAGO-treated sheep erythrocytes (SENAGO) were used in additional experiments. In parallel to the superior rosetting capacity of SE compared to HE. SENAGO were by themselves stimulatory, and the response was further enhanced by PEG or TPA. Antibody L180/1, specific for the T11 (CD2) target structure (T11TS) on SE, homologous to the human CD2 ligand LFA-3, abolished the response to SENAGO alone or when combined with PEG or TPA. The results suggest that ENAGO induce T-cell response through CD2-LFA-3-T11TS interaction, and via other surface antigens bound by the oxidatively induced aldehyde groups on ENAGO.
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PMID:Activation of human T cells by neuraminidase-galactose oxidase-treated erythrocytes involving CD2 (T11) and its complementary structure. 289 54

CD3+ WT31- T cells were sorted from peripheral blood of a normal healthy donor by a FACS IV and cloned by limiting dilution in the presence of a phorbol ester (tetradecanoyl phorbol acetate, TPA), calcium ionophore (ionomycin, Io), interleukin-2 (IL-2), allogeneic cells, and phytohemagglutinin (PHA). One of the derived clones, 290-2, was investigated in detail. 290-2 mediated strong natural killer (NK) but not lymphokine-activated killer (LAK) activity. It proliferated in the presence of IL-2 but not IL-4. It carried the surface phenotype CD3+ WT31- CD4weak+ CD8-, CD16-, and Leu 19+. Expression of CD4 was heterogeneous within the clone, since two of three subclones were also CD4weak+ but one was CD4-. NK activity was blocked by monoclonal antibody (moAb) to CD1 1a (LFA1), but not by monoclonal antibody (moAb) to either CD3 or CD4. Northern blotting revealed T-cell receptor (TCR-gamma) but not alpha- or full-length beta-chain mRNA. 290-2 proliferated autonomously when stimulated with a combination of TPA +Io, with PHA or CD3 moAb and autologous B-cell lines (B-LCL) (and this was inhibited by an anti-IL-2 receptor moAb), but not to allogeneic B-LCL or any of the other stimulating agents alone. Unexpectedly, the TPA + Io stimulus which resulted in maximal proliferative responses did not trigger interferon-gamma or granulocyte/macrophage colony-stimulating factor production, although both lymphokines were secreted in the presence of B-LCL + TPA + Io. Proliferative responses were not enhanced by the presence of B-LCL. Thus, activation signals sufficient for autocrine proliferative responses were insufficient for secretion of other lymphokines. Such clones will provide valuable reagents for investigating the biology of the TCR-gamma+ T cell.
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PMID:Different signals for stimulation of proliferation and lymphokine secretion by a CD3+ WT31- cloned cytotoxic lymphocyte. 296 87

Treatment of splenocytes and lymph node cells of 5 month-old MRL/lpr mice with TPA induced IL-2-dependent proliferation of the cells in the presence of CA++. The induced response was inhibited completely by a monoclonal antibody to IL-2 receptor. The combination of TPA and A23187 in the lpr cells induced both proliferation and production of IL-2 in a Ca++-dependent fashion. The proliferative response of the lpr cells was equivalent to that of congenic (MRL/+/+) or normal cells, but the quantity of IL-2 secreted from the lpr cells was significantly less than that of the controls. Actinomycin D, but not mitomycin C, blocked IL-2 secretion from the treated lpr cells indicating de novo synthesis of IL-2 mRNA in the cells. Thus the lpr lymphocytes can be activated to proliferate in response to IL-2, yet they do not secrete IL-2 at a normal level even if activation signals are transmitted into the cells.
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PMID:Interleukin-2 responses of MRL/lpr mouse splenocytes and lymph node cells induced by TPA and A23187. 310 64

We report here experiments on the analysis of cellular signal transduction in a series of patients with chronic B cell disorders (B cell chronic lymphocytic leukemia [B-CLL] and prolymphocytic leukemia). We compared the response of the leukemic cells with primary external signals (interleukin 2 [IL-2] or B cell differentiation factors [BCDF or IL-6]) with their response to secondary inducers (the phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA] or the calcium ionophore A23187) that circumvent the first part of the signal transduction pathway by directly activating the key enzyme protein kinase C. One BCDF was synthesized by mitogen-activated peripheral blood B lymphocytes; a second BCDF was constitutively produced by the human bladder carcinoma cell line T24. Changes in morphology, Tac (IL-2 receptor) expression, RNA synthesis measured by 3H-uridine uptake, and immunoglobulin production tested by enzyme-linked immunosorbent assay were used as parameters of successful signal transduction. TPA alone and TPA plus A23187 (synergistically) effectively initiated differentiation in all the leukemia cases. Neither IL-2 nor BCDF (singly or in combinations) caused equivalent responses. On the other hand, IL-2 and BCDF produced a substantial differentiation effect on normal B lymphocytes. Our data suggest that (a) B-CLL cells are able to respond to direct stimulation of the second messenger pathway (through protein kinase C) but not to the physiological stimuli IL-2 or BCDF; (b) the defect in signal transduction appears to be located upstream of protein kinase C (a possible candidate is a G protein); (c) malignant B cells may spontaneously or after treatment with inducers express the IL-2 receptor (Tac antigen) in the absence of a functional differentiating response to IL-2; and (d) signs of proliferation/differentiation in B-CLL samples after incubation with IL-2 or BCDF might be due to contamination of the cell populations with residual normal B cells.
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PMID:Analysis of signal transduction in B chronic lymphocytic leukemia cells. 312 49

Triggering of the T-cell receptor by anti-CD3 monoclonal antibodies (mAb), for example OKT3, induces accessory cell (AC)-dependent interleukin-2 (IL-2) and IL-2 receptor synthesis, and ultimately, T-cell proliferation. We report on the ability of a HLA-class I specific monomorphic mAb, namely FMC16, to inhibit OKT3-driven T-cell mitogenesis. FMC16 was apparently selective for OKT3 because it did not block Concanavalin A (Con A) or mAb Leu-4 induced proliferation. Moreover, this effect was not due to non-specific toxicity nor interference with OKT3 binding. Kinetic analysis showed that FMC16 was inhibitory when added up to 24 hr after initiation of culture. FMC16 drastically reduced both IL-2 production and IL-2 receptor expression, but did not interfere with IL-2 responsiveness. The inhibitory effects were not altered by the addition of exogenous IL-2 if FMC16 was present at the beginning of culture; however, IL-2 did restore proliferation if FMC16 was not added until 3 to 6 hr after initiation of culture. This coincided exactly with an IL-2 mediated increase in the level of TAC-positive cells. Furthermore, T-cell activation triggered by the synergistic action of OKT3 and a phorbol ester (TPA) in the absence of AC was also blocked by FMC16, suggesting that inhibition was not AC-dependent. Taken together, these results indicate that FMC16 interferes with early signals leading to IL-2 production and IL-2 receptor expression and suggest that HLA-class I determinants play an early role in T-cell activation.
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PMID:Specific inhibition of OKT3-driven T-cell mitogenesis by an anti HLA-class I monoclonal antibody. 326 8

Three monoclonal antibodies (mAb), of IgG1, IgG2a, and IgM isotypes, raised against the T3 complex, were used to probe the activation of human T cells. The IgM antibody 235 was not mitogenic for peripheral blood mononuclear cells (PMC). It efficiently blocked the proliferation of PMC induced by T cell mitogens, alloantigens, and soluble antigens. The other two antibodies were mitogenic, and behaved similarly to Leu 4 and OKT3, respectively. In T cell preparations with less than 0.1% monocytes (as assayed by nonspecific esterase staining), all three mAb were not mitogenic. They failed to induce either interleukin 2 (IL-2) receptor expression or IL-2 secretion. Addition of IL-1 failed to collaborate with anti-T3 mAb to induce these T cells to proliferate, but IL-2 enhanced T cell proliferation slightly. Monocyte-depleted T cells, however, proliferated in response to all three anti-T3 mAb, when TPA was added, in a dose-dependent manner. TPA induced a low level of IL-2 receptor expression in monocyte-depleted T cells, without inducing IL-2 secretion. Anti-T3 plus TPA induced a marked enhancement in both quantity and intensity of IL-2 receptor expression. IL-2 secretion was also detected. These results indicate that anti-T3 IgM can deliver an inductive signal despite its blockage of T cell proliferation, and that two signals are necessary and perhaps sufficient to induce human T cell activation and proliferation.
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PMID:Human T cell activation. I. Monocyte-independent activation and proliferation induced by anti-T3 monoclonal antibodies in the presence of tumor promoter 12-o-tetradecanoyl phorbol-13 acetate. 392 Mar 41

TBSA 10%III degrees burn mice model was used. The changes in free calcium concentration ([Ca2+]i) and protein kinase C (PKC) activity in activated T cells from burn mice, and their relationship with T cell functions was studied. The results showed that [Ca2+]i and PKC activity in activated T cells were reduced after burn and these changes were closely related to reduced interleukin 2(IL-2) mRNA and IL-2 receptor alpha (IL-2R alpha) mRNA levels, decreased IL-2 production, suppressed IL-2R alpha expression, reduced T lymphocytes transformation in T cells of burn mice. Calcium cation ionophore A 23187 and PKC activator TPA could in vitro elevate respectively [Ca2+]i and PKC activity in activated T cells of burn mice. They also increased significantly IL-2 and IL-2R alpha gene expression in T cells of burn mice, but not up to the normal control. It is suggested that reduced [Ca2+]i, PKC activity in activated T cells may be one of the causes which produce suppression of T cell functions after burns.
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PMID:[Changes in free calcium concentration and protein kinase C activity in activated T cells of burn mice and their significance]. 873 3


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