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

Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c-myc, c-fos, IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.
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PMID:Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. 254 May 28

Human peripheral blood monocytes (Mo) synthesize prostaglandin E2 (PGE2) when activated with lipopolysaccharide (LPS). This production is strongly enhanced by the addition of supernatant from phytohaemagglutinin (PHA)-activated T cells. To evaluate the factor(s) responsible for this enhancement we studied the effect of several cytokines on the PGE2 metabolism. Recombinant interleukin-1 (IL-1) or recombinant IL-2 strongly enhanced PGE2 synthesis in LPS-stimulated Mo cultures, whereas recombinant interferon-gamma (IFN-gamma) partially inhibited its production. To see whether the effect of IL-2 on Mo was due to the presence of IL-2 receptor (IL-2R) on the cell surface, flow cytometric analysis and electron microscopy were used to investigate IL-2R expression in unstimulated and stimulated Mo. Stimulated, but not resting, Mo displayed the p55 IL-2R chain on their cellular surface and associated with the polyribosomes of the rough endoplasmic reticulum in the cytoplasm. This finding strongly suggested that the p55 chain of the IL-2R was synthesized by activated Mo. To confirm this result, 125I-labelled IL-2 was bound under high- and low-affinity conditions and cross-linked to Mo cultured in the presence of LPS, IFN-gamma or IL-1. The cross-linked 125I-IL-2/IL-2R complexes were analysed by SDS-PAGE. Mo cultured with LPS, IFN-gamma and IL-1 expressed the p55 protein detected by low-affinity cross-linking, whereas only LPS-stimulated Mo displayed a barely detectable band with an apparent MW of 70,000 under high-affinity binding conditions. In addition, stimulated Mo were found capable of producing the soluble form of IL-2R. Finally, LPS-activated Mo only responded to the addition of IL-2 by an increase in PGE2 production, suggesting that the function of IL-2R on activated Mo is linked to the stimulus applied.
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PMID:The expression of functional IL-2 receptor on activated macrophages depends on the stimulus applied. 266 16

Studies are reviewed, which establish a novel regulatory role for the T cell surface molecule CD2 and the T cell lymphokine IL-2: Immunoregulation of hematopoiesis. IL-2 induces a receptor-specific inhibition of early erythroid progenitors. IL-2-induced inhibition of erythropoiesis is mediated by interferon-gamma protein release and is associated with interferon-gamma mRNA accumulation. CD3-triggered p55 IL-2 receptor expression is a prerequisite for IL-2-induced erythropoietic inhibition and is associated with p55 mRNA synthesis. Hematopoietic effects of IL-2 are mediated by CD2/LFA-3 receptor ligand interactions. The studies demonstrate that the regulatory roles of IL-2 and CD2 extend beyond governance of the immune system itself and can subserve to control red cell production in vitro.
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PMID:T cell regulated hematopoiesis--molecular interactions in hematopoietic control by CD2 and interleukin 2. 290 89

Once stimulated with Toxoplasma gondii or cytomegalovirus (CMV) antigens, peripheral blood mononuclear cells from healthy seropositive donors secrete comparable levels of interferon-gamma (IFN-gamma). Both antigens also stimulated specific production of interleukin 2 (IL-2), a lymphokine believed to be important in IFN-gamma generation. T. gondii antigen, however, induced ninefold more IL-2 than did CMV antigen suggesting different mechanisms for antigen-stimulated IFN-gamma production. Therefore, we examined for both antigens 1) the cellular sources of IL-2 and IFN-gamma, 2) the kinetics of IL-2 production and IL-2 receptor (IL-2R) expression, and 3) the effect of antibodies to IL-2 and IL-2R on IFN-gamma secretion. For both antigens, IL-2 and IFN-gamma secretion was T4+ cell-dependent. T. gondii antigen induced high levels of IL-2 at 24 hr which increased further at 48 hr, and IFN-gamma production was strongly inhibited by antibodies to both IL-2 (90 +/- 2%) and IL-2R (80 +/- 5%). In contrast, CMV antigen stimulated low levels of IL-2 at 24 hr which declined still further by 48 hr, and CMV-stimulated IFN-gamma generation was appreciably less well inhibited by antibodies to IL-2 (47 +/- 2%) and IL-2R (31 +/- 8%). These results suggest the possibility of two mechanisms for antigen-induced IFN-gamma production--one primarily dependent on and the other largely independent of IL-2 and its receptor. Both mechanisms, however, require the activity of sensitized T4+ cells.
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PMID:Antigen-induced human interferon-gamma production. Differential dependence on interleukin 2 and its receptor. 295 45

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

Anti-Tac antibody, which binds to the interleukin 2 (IL-2) receptor and thus blocks IL-2 binding to and activation of T lymphocytes, was used to investigate the role of IL-2 in interferon-gamma (IFN-gamma) production. Three T-cell mitogens (phytohemagglutinin, concanavalin A, and the pan-T monoclonal antibody OKT3) were used as IFN-gamma inducers. In each case, anti-Tac antibody clearly inhibited IFN-gamma production. This occurred even under conditions where cellular proliferation (as measured by incorporation of [3H]thymidine) was only slightly inhibited. The inhibitory effects of anti-Tac were reversed by the addition of purified IL-2. Therefore, endogenous production of IL-2 and its binding to the IL-2 receptor are needed for maximum IFN-gamma production.
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PMID:Interleukin 2 receptor blockade by anti-Tac antibody inhibits IFN-gamma induction. 300 Jun 25

Large granular lymphocytes (LGL), which consist of a unique population comprising almost all of the natural killer (NK) cell activity, were separated from peripheral blood mononuclear cells by sequential depletion of monocytes and conventional discontinuous Percoll density gradient sedimentation. The LGL populations thus obtained exhibited significant levels of interferon-gamma (IFN-gamma) production and proliferation, as well as augmentation of NK cell activity in response to interleukin-2 (IL-2). Among these IL-2-driven phenomena, only IFN-gamma production was markedly inhibited by the monoclonal anti-Tac antibody, which presumably recognized the IL-2 receptor, whereas the proliferative response and the augmentation of NK cell activity were only minimally affected by the same antibody, even at the higher concentration. The dissociation of the effects of anti-Tac antibody on these IL-2-driven events gives us some insight on the role of IL-2 receptors involved in these immunologically interesting functions of IL-2.
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PMID:Effects of anti-Tac antibody on the response of large granular lymphocytes to interleukin-2. 300 67

Interleukin-2 (IL-2) is a lymphokine that plays a crucial role in the immune system, especially in the growth control of T lymphocytes. Expression of this lymphokine is restricted to activated T lymphocytes. Here we demonstrate the presence of unique DNA sequences in the 5' flanking region of the human IL-2 gene that control induced T-cell-specific gene expression. We also show that the DNA sequences function in an orientation-independent manner and activate a heterologous promoter which is otherwise inert in induced T cells. The DNA, which spans about 200 bp, contains regions with sequence homology to LTR sequences of HTLV-III (or LAV) and the 5' upstream region of the IL-2 receptor and interferon-gamma genes.
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PMID:Regulation of human interleukin-2 gene: functional DNA sequences in the 5' flanking region for the gene expression in activated T lymphocytes. 301 13

Phorbol ester phorbol myristate acetate (PMA) induces proliferation in nonmalignant human B cells and B cells from a patient with B prolymphocytic leukemia (B-PLL). Mitogen-free T cell-derived conditioned medium acts synergistically with PMA in inducing proliferation of B-PLL cells but does not enhance the PMA-stimulated outgrowth of nonmalignant B cells. Interleukin 2 (IL-2) has no effect on the outgrowth of B-PLL cells, and monoclonal antibodies against the IL-2 receptor do not influence the response to PMA and conditioned medium. Recombinant interferon-gamma (IFN-gamma), in contrast, is a potent enhancer of PMA-induced proliferation of B-PLL cells. With gel filtration techniques and with the use of anti-IFN-gamma antibodies, it is shown that IFN-gamma in the conditioned medium is responsible for the observed increase in B-PLL cell proliferation. Preincubation of B-PLL cells with IFN-gamma induces responsiveness to PMA, whereas IFN-gamma alone had no effect on these cells when pretreated with PMA. The combined data show that, in the presence of PMA, native and recombinant IFN-gamma are growth factors for B cells from a B-PLL patient and that IL-2 is not involved in this process.
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PMID:Induction of proliferation of B prolymphocytic leukemia cells by phorbol ester and native or recombinant interferon-gamma. 311 13

Peripheral blood lymphocytes from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), Reiter's disease, osteoarthritis, and from healthy volunteers were investigated for interferon-gamma (IFN-gamma) production after mitogen activation. Phytohaemagglutinin stimulation revealed an impaired IFN-gamma production in RA, SLE, and PSS but normal levels in Reiter's disease and osteoarthritis. In RA this deficiency was also seen after pokeweed mitogen, OKT3, and concanavalin A activation. No major differences were found in interleukin 2 (IL-2) production and cell proliferation. The IL-2 receptor expression was reduced on stimulated RA lymphocytes. The deficient IFN-gamma production was compensated in RA by co-stimulation of PHA or OKT3 with phorbol myristic acetate (PMA). In addition, the combination of the calcium ionophore A 23187 and PMA induced a strong IFN-gamma secretion in all patient groups and in the controls.
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PMID:Impaired mitogen-induced interferon-gamma production in rheumatoid arthritis and related diseases. 312 62


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