UNIPROT:P14784 - FACTA Search

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

It is well-known that the most prominent age-related immunological abnormalities were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigens. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample. The sixth, the combined stimulation with PMA and ionomycin could induce proliferative response to highly purified T cells, T cell subsets and B cells. The degree of age-related decline of the proliferative response of CD-8 positive T cells was most significant, that of CD-4 positive ones was next and that of B cells was least. The seventh, although the maximum of c-myc mRNA level was attained at 2 hr after the stimulation and similar amount between the both age groups, the amount of mRNA at 8 or 24 hr was rather higher in the aged T cells than in the young ones. The reduction of the degradation rate of c-myc mRNA seemed to be the cause. We found no difference of the maximum amount and kinetics of c-myb mRNA between both age groups in T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The characteristic changes of immune function with aging]. 281 Oct 4

The effect of polyclonal (anti alpha and beta chain) and monoclonal (anti alpha-chain) antibodies against lymphocyte function-associated antigen 1 (LFA-1) on T cell activation was studied. When added at the beginning of activation but not after 24 h or later the antibodies as well as the F(ab')2 or Fab fragments of polyclonal antibodies inhibited concanavalin A (Con A)-induced proliferation, interleukin 2 (IL-2) production, and the expression of receptors for IL-2 and transferrin. The inhibitory effect reached a maximum at the same time as optimal proliferation (72 h). Inhibition of proliferation lasted for 5 days or longer, although IL-2 production was only inhibited during the first 48 h of culture. Receptors for IL-2 and transferrin were re-expressed to the original level after 3 days of activation. Addition of external IL-2 at the beginning of the anti-LFA-1 containing culture prevented the inhibition of IL-2 receptor expression, while inhibition of transferrin receptor expression was unaffected, supporting the conclusion that the expression of these two receptors is regulated by partially independent signals. The polyclonal and monoclonal anti-LFA-1 antibodies also inhibited phorbol ester (PMA)-dependent OKT3 activation of highly purified T cells. The results suggest that the LFA-1 antibodies block an early step in the reactions necessary for IL-2 production, and that the LFA-1 molecule participates not only in T cell-accessory cell interaction but also in T-T interaction during the early phases of the activation process.
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PMID:Studies on the role of lymphocyte function-associated antigen 1 (LFA-1) in T cell activation. 312 61

The inhibitory effects of CsA in cell-mediated immunity are well known. There is controversy about whether CsA directly inhibits the function of accessory cells as well as T lymphocytes. We have used northern blotting to compare the effects of CsA on several human monocyte and T cell mRNAs, and we have performed "CsA-pulsing" experiments to separately evaluate the effect of the drug on accessory and T cells during lymphocyte mitogenesis. CsA blocked the induction of several lymphokine mRNAs in stimulated T cells including IL-2, IFN-gamma, and IL-4. CsF, an analog that is ten times less active than CsA as an immunosuppressant, was some ten times less active in inhibiting lymphokine gene expression in culture. CsA and CsF had little effect on the mRNA for the 55 KD low-affinity IL-2 receptor, but there was decreased expression of the TAC antigen. Exogenous IL-2 reversed the CsA-mediated suppression of cell proliferation and TAC expression. This indicates that the primary block with cyclosporines is at the level of lymphokines rather than lymphokine receptors. CsA did not reduce the levels of several monocyte mRNAs, however. These included c-myc and Il-1 alpha/beta mRNAs, induced by PMA plus Con A, as well as HLA-DR alpha and gamma-Ip10 mRNAs in monocytes treated with IFN-gamma. When monocytes were pulsed with CsA, there was no reduction in their subsequent accessory function for anti-CD3 and lectin responses. T lymphoblasts pulsed with CsA, however, did not proliferate or release growth factor. Likewise in the primary MLR between dendritic cells and T cells, dendritic cells were not impaired following pulsing with CsA, whereas treated T cells made 70% less IL-2. The primary site of action of CsA therefore seems to be the production of lymphokines by T lymphocytes.
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PMID:Evidence that cyclosporine inhibits cell-mediated immunity primarily at the level of the T lymphocyte rather than the accessory cell. 313 67

Peripheral blood mononuclear cells from 15 patients with alcoholic cirrhosis (AC) and 15 matched healthy controls were tested for their proliferative response to mitogens such as PHA and con A, tumour promoter PMA and OKT3 monoclonal antibody, for their capacity to produce IL-2 and to respond to recombinant IL-2 (rIL-2). The expression of IL-2 receptor (Tac) together with two other activation markers, the receptor for transferrin (T9) and Ia antigen have also been assessed. A profound decrease of proliferative response was observed after stimulation by lectins and PMA. IL-2 production was significantly decreased (0.39 +/- 0.07 versus 0.82 +/- 0.009 units; P less than 0.001) in alcoholic cirrhosis. Resting PBMC of these patients disclosed spontaneous responsiveness to rIL-2 without requiring prestimulation with PHA as observed in healthy subjects. This abnormal response was associated with significantly increased percentages of Tac (19.4 +/- 3.1 versus 5.1 +/- 1.1%; P less than 0.001), T9 (13.6 +/- 3.3 versus 6.6 +/- 1.1%; P = 0.04) and Ia positive cells (21.4 +/- 5.4 versus 11.5 +/- 1.4; P less than 0.05) in alcoholic cirrhosis. Defective proliferative activity and impaired IL-2 production, combined with an increase of lymphocytes bearing T cell activation markers and of rIL-2 responsiveness could represent in vitro correlates for mechanisms leading to immunoregulatory disturbances in cirrhotic patients.
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PMID:Decreased proliferative activity associated with activation markers in patients with alcoholic liver cirrhosis. 326 58

Virus free supernatants (VFS) obtained by ultracentrifugation of homogenates of African swine fever (ASF) virus infected cultures inhibited the proliferative response and the expression in peripheral blood mononuclear cells of two activation molecules, the IL-2 receptor (IL-2R) and the swine MHC class II antigens (SLA II), induced by several stimuli (lectins, PMA plus the calcium ionophore A23187 or specific antigen). This inhibition was time dependent: no effect was seen on IL-2R expression when VFS was added after 48 h, when the expression of this molecule reached its maximum. However at this time the proliferative response was still inhibited. The presence of VFS in the cultures was necessary to inhibit both the IL-2R expression and the proliferation of cells. In these conditions the addition of exogenous IL-2 to the cultures failed to restore the IL-2R expression and the proliferation shown by control stimulated cells. Furthermore, the IL-2 activity found in supernatants from cell cultures stimulated with Con A in the presence of VFS was even higher than in cultures stimulated without VFS. The inhibition observed suggests an important impairment of host immunocompetence in ASF infected swine.
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PMID:Inhibition of IL-2R and SLA class II expression on stimulated lymphocytes by a suppressor activity found in homogenates of African swine fever virus infected cultures. 761 79

Helicobacter pylori colonization of the human gastric mucosa causes a long-term, not self-limiting inflammation, suggesting that the microbe has properties to protect itself against the host immune defence system. Recently we were able to demonstrate that H. pylori suppresses the in vitro proliferative response of human peripheral blood mononuclear cells to antigens as well as to mitogens without affecting cell viability. The purpose of this study was to clarify which cell subsets of mononuclear cells are influenced by H. pylori. The use of monocytes which had been pretreated with a soluble cytoplasmic fraction of H. pylori (30 micrograms ml-1) led to a suppressed proliferation of T cells after PHA-activation. Activation of isolated T cells with PHA and PMA revealed that the proliferative response of lymphocytes could also be inhibited independently of monocytes. The anti-proliferative effect was associated with a reduction of IL-2 receptor (CD25) expression as well as an inhibition of blastogenesis. Furthermore, the spontaneous proliferation of EBV-transformed B cell lines was suppressed in a dose-dependent manner. FACS-analysis of HLA-DR, ICAM-1 and CD14 expression on the surface of monocytes revealed an influence of H. pylori on CD14 expression at a concentration of 30 micrograms ml-1, while the expression of HLA-DR and ICAM-1 was not affected at this concentration.
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PMID:Suppression of human mononuclear cell response by Helicobacter pylori: effects on isolated monocytes and lymphocytes. 790 99

Activation of protein kinase C (PKC) in T cells leads to a variety of responses including IL-2 production and IL-2 receptor expression. PKC consists of several isoforms that exhibit some different in vitro properties. We have set up a Western blotting system to explore the regulation of PKC isoforms during T cell activation. In Jurkat T lymphoma cells, PKC alpha, beta, delta, epsilon, and zeta were detected. PKC alpha and beta existed primarily in the cytosol, translocated to the membrane fraction after 10 minutes of treatment with PMA, and almost completely disappeared within 16 h. A larger fraction of PKC delta and epsilon existed in the membrane fraction compared to PKC alpha or beta, and PKC epsilon translocated to the membrane fraction rapidly. Translocation of PKC delta was not apparent after 1 h treatment with PMA, but total PKC delta protein was reduced within 4 to 6 h of treatment. Consistent with this, overnight treatment with PMA caused down-regulation of both PKC delta and epsilon, but to a lesser degree than was observed with PKC beta. Anti-PKC zeta antibody detected two bands at 82 and 75 kDa. The 75-kDa band existed mostly in the cytosol fraction and showed no translocation or down regulation after PMA. We present evidence that this 75-kDa band represents PKC zeta. Similar PMA-induced translocation responses were observed in murine thymocytes showing that the responses are not unique to PKC isoforms in Jurkat. These results demonstrate that it is possible for the PKC isoforms to be differentially regulated during T cell activation.
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PMID:Regulation of protein kinase C isoform proteins in phorbol ester-stimulated Jurkat T lymphoma cells. 843 13

Although the role of CD28 in T cell costimulation is firmly established, the mechanisms by which it exerts its costimulatory actions are less clear. In many circumstances it is difficult to distinguish the effects of CD28 from subsequent actions of cytokines, such as IL-2, on T cell proliferation. Here, we report a model of CD28 costimulation using PMA plus the natural ligand CD80 that resulted in very limited stimulation of IL-2, as evidenced by both cytokine production and IL-2 promoter stimulation. Promoter assays revealed CD28-dependent effects on both NF-kappaB and AP-1, but not on NF-AT or the intact IL-2 promoter. In addition, T cell proliferation was completely resistant to the actions of the immunosuppressant cyclosporin A (CsA). Moreover T cell proliferation was unaffected by the addition of blocking Abs to both IL-2 and the IL-2 receptor, demonstrating that this form of costimulation by CD28 was independent of IL-2. We also investigated the effects of stimulating T cell blasts with CD80 alone and found that there was a limited requirement for IL-2 in this system. We conclude that CD28 costimulation can cause substantial T cell proliferation in the absence of IL-2, which is driven by a soluble factor independent of NF-AT transactivation.
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PMID:IL-2-independent activation and proliferation in human T cells induced by CD28. 1043 13

The factors determining the growth and survival of cells in B chronic lymphocytic leukemia (CLL) have remained poorly understood. We investigated the effects of optimal mitogen combinations (OMCs) on the expression of 26 surface membrane antigens among 33 CLL patients. The seven OMCs used were selected after pre-testing 14 combinations of (1) S. aureus Cowan I (SAC), (2) interleukin-2 (IL-2), (3) tumor necrosis factor alpha (TNF-alpha) and (4) 12-O-tetradecanoylphorbol 13-acetate (TPA; also known as phorbol 12-myristate 13-acetate or PMA). In flow cytometry we revealed that OMCs induced statistically highly significant upregulation of the expression of CD5, CD11c, CD19, CD22, CD23, CD25, CD38, CD40, CD45, CD45RO, CD95, CD126, CD130 and FMC7, and downregulation of CD20 and CD124 expression. Interestingly, the expression of CD27, CD45RA, CD79b, CD80, CD122 and that of the immunoglobulin gene superfamily members CD21, Ig-kappa, Ig-lambda, Ig-delta and Ig-micro were not significantly affected under similar conditions. The expression of several antigens was co-regulated, suggesting common regulatory pathways. These antigens include CD11c/CD5, CD11c/CD22, CD11c/CD126, CD11c/FMC7 as well as CD27/CD45, CD27/CD45RA and CD27/CD79b. Upregulation of surface antigen expression, induced by OMCs, should be applicable in antibody therapy in vitro and in vivo, and in negative stem cell selection for autotransplantation. Furthermore, the current strategy to enhance cell surface antigen expression may be a versatile tool to raise humoral and cell-mediated host defense against CLL cells. Upregulation of proteins mediating positive growth signals (eg CD25, CD40) and negative signals or apoptosis (eg CD95) may be used to sensitize cells to chemotherapy and programmed cell death.
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PMID:Surface membrane antigen expression changes induced in vitro by exogenous growth factors in chronic lymphocytic leukemia cells. 1220 Jun 83

TGF-beta1 plays an important role in the maintenance of immune homeostasis and self-tolerance. To determine the mechanism by which TGF-beta1 prevents autoimmunity we have analyzed T cell activation in splenic lymphocytes from TGF-beta1-deficient mice. Here we demonstrate that unlike wild-type splenic lymphocytes, those from Tgfb1(-/-) mice are hyporesponsive to receptor-mediated mitogenic stimulation, as evidenced by diminished proliferation and reduced IL-2 production. However, they have elevated levels of IFN-gamma and eventually undergo apoptosis. Receptor-independent stimulation of Tgfb1(-/-) T cells by PMA plus ionomycin induces IL-2 production and mitogenic response, and it rescues them from anergy. Tgfb1(-/-) T cells display decreased CD3 expression; increased expression of the activation markers LFA-1, CD69, and CD122; and increased cell size, all of which indicate prior activation. Consistently, mutant CD4(+) T cells have elevated intracellular Ca(2+) levels. However, upon subsequent stimulation in vitro, increases in Ca(2+) levels are less than those in wild-type cells. This is also consistent with the anergic phenotype. Together, these results demonstrate that the ex vivo proliferative hyporesponsiveness of Tgfb1(-/-) splenic lymphocytes is due to prior in vivo activation of T cells resulting from deregulated intracellular Ca(2+) levels.
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PMID:TGF-beta 1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes. 1270 39

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