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

Early intracellular signals in response to anti-Leu4 in T cells were studied. There are two groups whose T cells, in the presence of accessory cells, proliferate (responders) or not (nonresponders) in response to anti-CD3 antibodies of the subclass IgG1, as is the case with anti-Leu4. Approximately 30% of Protein Kinase C (PKC) in the cytosol fraction disappeared temporarily, thereby indicating PKC activation, in response to immobilized anti-Leu4. PKC activation in purified T cells was detected both in responders and in nonresponders. The stimulation by anti-Leu4 crosslinked with goat anti-mouse IgG led to an increase in intracellular free calcium concentration [Ca++]i) in the T cells, and this increase was identical in responders and nonresponders. Although minimal Interleukin 2 (IL-2) receptor expression was apparent, T cells even from responders failed to proliferate in response to anti-Leu4, in the absence of accessory cells. Thus, in T cells from responders or nonresponders, anti-Leu4 stimulation induces early intracellular signal transduction and IL-2 receptor expression, but without accessory cells, proliferation does not occur.
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PMID:Early intracellular events in human T cells induced by anti-Leu4 antibody: comparison between responders and nonresponders. 196 71

Interleukin 2 (IL-2) is a lymphokine, produced by T cells upon antigenic or mitogenic stimulation, that is a critical regulator of T-cell proliferation. Although the binding of IL-2 to its receptor has been well characterized, the molecular mechanisms by which IL-2 transmits its signal from the membrane to the interior of the cell are poorly understood. Like most other growth factors, IL-2 causes rapid phosphorylation of proteins within its target cells. Unlike many other growth factors, however, the known subunits of the IL-2 receptor lack tyrosine-specific kinase activity, and little is known about the kinases whose activities are regulated by IL-2. Here we show that IL-2 (but not IL-4) induces rapid phosphorylation of the p72-74 serine/threonine-specific kinase encoded by the c-Raf-1 protooncogene in an IL-2-dependent murine T-cell line, CTLL-2, and that this phosphorylation is associated with increased kinase activity in p72-74 Raf-1-containing immune complexes. The concentration dependence of IL-2-mediated elevations in Raf-1 kinase activity correlated well with IL-2-stimulated proliferation of CTLL-2 cells. Furthermore, much of the IL-2-stimulated phosphorylation of p72-74 Raf-1 occurred on tyrosines. To our knowledge, the Raf-1 kinase represents the first endogenous substrate of an IL-2-regulated tyrosine kinase to be identified.
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PMID:Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1 kinase in a T-cell line. 199 24

Interleukin 2 (IL-2) is a potent growth factor for T lymphocytes, playing a crucial role in the immune response. In view of the considerable evidence that the immunoregulatory cytokines (or lymphokines) also play a role in the growth and differentiation of cells in the central nervous system (CNS), we examined the operation of the IL-2 system in a cell line of CNS origin by expressing a cDNA encoding the beta chain of the human IL-2 receptor (IL-2R beta, a 75-kDa protein). When the cDNA was expressed in a human oligodendroglioma cell line, ONS-21, the IL-2R beta bound IL-2 with an affinity similar to that in lymphoid cells (Kd, approximately 2 nM). Furthermore, cell proliferation ([3H]thymidine incorporation) was stimulated by IL-2. These results demonstrate that the same cytokine receptor is functional in cells of the immune system and CNS and point to a molecular mechanism that is similar for growth-signal transduction between lymphoid and neural cells but that may be different in other cells, such as fibroblasts.
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PMID:Interleukin 2 receptor beta chain expressed in an oligodendroglioma line binds interleukin 2 and delivers growth signal. 239 60

Gangliosides have been shown to suppress human and murine lymphocyte proliferative responses in vitro. We tested the suppressive effects of gangliosides on the proliferation of autoreactive lymphoid cells obtained from Lewis rats with experimental allergic encephalomyelitis (EAE). Exogenous rat brain gangliosides inhibited both antigen- and mitogen-induced proliferation by as much as 79 and 93%, respectively. Gangliosides similarly inhibited the antigen-induced proliferation of a myelin basic protein (MBP)-reactive T-cell line which is able to passively induce EAE. Suppression was greatest when gangliosides were added at the initiation of culture, and was not abrogated by supraoptimal antigen concentration. Interleukin 2 (IL-2) activity in culture supernatants was not diminished by the addition of gangliosides. Gangliosides did not inhibit the IL-2-induced proliferation of a murine IL-2-dependent cell line, CTLL-20, unless the IL-2 was first preincubated with gangliosides before the addition of CTLL-20. Preincubation of CTLL-20 with gangliosides resulted in no inhibition of the subsequent responses to IL-2. Exogenous gangliosides did not decrease the binding of a monoclonal antibody directed against the rat cell surface IL-2 receptor. Addition of exogenous IL-2 to ganglioside-suppressed cultures had no effect or only partially restored the proliferative responses. Therefore, gangliosides were shown to inhibit the proliferation of autoreactive lymphoid cells without affecting IL-2 production or IL-2 receptor expression.
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PMID:Gangliosides suppress the proliferation of autoreactive cells in experimental allergic encephalomyelitis: ganglioside effects on IL-2 activity. 243 55

Interleukin 2 (IL-2) is a secreted glycoprotein which acts as an activation and proliferative signal for lymphocytes expressing membrane-bound glycoprotein IL-2 receptors. We have recently established that swainsonine (SW), an inhibitor of mannosidase II during N-linked glycoprotein processing, augmented mitogen-induced mononuclear leukocyte IL-2 receptor expression and IL-2-induced proliferation. The objective of the present investigation was to examine the effect of SW on lymphokine-activated killer (LAK) cell induction. Human mononuclear leukocytes were treated with various concentrations of SW (0.1-10 micrograms/ml) and IL-2 (1-100 units/ml) for up to 72 h. SW augmented IL-2-induced LAK activity directed against human lung carcinoma, melanoma, and leukemia cells 2-3-fold. LAK activity generated in the presence of SW at suboptimal doses of IL-2 (10 units/ml) was similar to that observed with higher concentrations of IL-2 (100 units/ml) alone. SW treatment alone or in combination with IL-2 increased the percentage of IL-2 receptor-positive cells. Furthermore, pretreatment with SW subsequently enhanced IL-2-induced lymphocyte proliferation. SW-treated mononuclear leukocytes exhibited an increase in high-mannose type glycoproteins based upon [3H]mannose labeling, susceptibility to alpha-mannosidase, and binding to concanavalin A-Sepharose. These results indicate that modulators of glycoprotein processing may be useful in lowering the concentrations of IL-2 required for LAK induction and maintenance.
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PMID:Potentiation of human lymphokine-activated killer cell activity by swainsonine, an inhibitor of glycoprotein processing. 250 Oct 20

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

Interleukin 2 and its receptor have emerged as a central control system in the regulation of the immune response and the proliferation of T cells, B cells, and macrophage. IL-2 receptor expression is strongly associated with several forms of human lymphoproliferative disease including adult T-cell leukemia-lymphoma, hairy cell leukemia, Hodgkin's disease, and peripheral T-cell lymphoma in which it may play a pathogenetic role. IL-2 receptor expression may also play a role in some B-cell non-Hodgkin's lymphomas and histiocytic proliferations. Recent discoveries in immunology and advances in biotechnology have opened therapeutic possibilities for IL-2 including the use of anti-Tac monoclonal antibodies and immunoconjugates for the therapy of Tac-positive lymphoproliferative disease, the use of anti-Tac monoclonal antibodies as novel immunosuppressants, and the use of genetically engineered recombinant IL-2 and activated autologous lymphocytes in the adoptive immunotherapy of cancer. Therapeutic and diagnostic applications of IL-2 continue to be defined.
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PMID:Interleukin receptors in lymphoid lesions. Relevance to diagnosis, biology, and therapy. 267 80

The production and targeting of a major T cell derived lymphokine, Interleukin 2 (IL-2), were studied in 23 uremic patients undergoing regular hemodialysis treatment and 20 uremic patients prior to the onset of renal replacement therapy. In hemodialyzed patients, abnormally increased proportions of circulating T cells spontaneously expressing high affinity IL-2 receptors (IL-2 Rec) were detected: they bound a monoclonal antibody specifically directed to the IL-2 Rec 55 kDa chain (Tac antigen) (mean +/- SEM: 7.12 +/- 0.81% in patients vs. 2.15 +/- 0.39% in normal controls, P less than 0.0001) and significantly proliferated in presence of human recombinant IL-2 alone (mean +/- SEM: 5438 +/- 729 cpm in patients vs. 1647 +/- 244 cpm in normal controls). Hemodialyzed patients also exhibited significantly increased serum levels of soluble IL-2 receptor (mean +/- SEM: 4036 +/- 947 U/ml in patients vs. 253 +/- 29 U/ml in normal controls. P less than 0.001). Moreover, a significantly decreased IL-2 activity was detected in the supernatants of stimulated T cells from hemodialyzed patients (mean +/- SEM: 0.93 +/- 0.12 U/ml in patients vs. 2.49 +/- 0.22 U/ml in normal controls, P less than 0.0001). In nine hemodialyzed patients who were analyzed before and immediately after the hemodialysis session no acute modifications of the various parameters analyzed were detected. Although less profound, a similar pattern of T cell abnormalities was observed in the uremic non-hemodialyzed patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo T cell preactivation in chronic uremic hemodialyzed and non-hemodialyzed patients. 268 33

Interleukin 2 (IL-2) receptor expression was examined on recombinant IL-2 (rIL-2)-propagated tumor-infiltrating lymphocytes (TIL) from eight metastatic melanoma and three sarcoma samples. All 11 TIL expanded with similar growth rates. rIL-2 propagated TIL from five of eight metastatic melanoma specimens contained no Tac antigen-positive lymphocytes as determined by immunofluorescence and flow cytometry performed multiple times during the 4 to 8 week culture period. However, "Tac-negative" TIL did express the non-Tac IL-2-binding peptide, p70-75 as determined by [125I]IL-2 cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IL-2-binding assays revealed that these "Tac-negative" TIL expressed only an intermediate affinity IL-2 receptor. In contrast, TIL from the other three of eight melanoma and all three sarcoma contained one-third Tac-positive cells as assessed by flow cytometry analysis, and expressed surface non-Tac (p70-75) and Tac (p55) peptides by [125I]IL-2 cross-linking. These "Tac-positive" TIL displayed both the high and intermediate affinity IL-2 receptors. However, rIL-2-dependent growth of both "Tac-negative" and "Tac-positive" TIL was significantly inhibited by anti-Tac mAb, suggesting a transient Tac expression on the "Tac-negative" TIL. Additionally, due to the limits of our methodology, we cannot rule out the possibility of a constitutive expression of a low level of Tac, with an indicible expression of higher levels. Addition of culture supernatants from phytohemagglutinin- and phorbol myristate acetate-stimulated peripheral blood mononuclear cells to the "Tac-negative" TIL-induced detectable Tac expression within 48 h. These results indicate that both non-Tac and Tac IL-2 receptors play important roles during IL-2-dependent proliferation of TIL.
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PMID:Involvement of both Tac and non-Tac interleukin 2-binding peptides in the interleukin 2-dependent proliferation of human tumor-infiltrating lymphocytes. 278 85

The gene encoding the human Interleukin 2 (IL-2) receptor consists of 8 exons spanning more than 25 kilobases on chromosome 10. Exons 2 and 4 were derived from a gene duplication event and unexpectedly also are homologous to the recognition domain of human complement factor B. Receptor gene transcription is initiated at two principal sites in normal activated T cells. Adult T cell leukemia cells infected with HTLV-I show activity at both of these sites, but also at a third transcription initiation site. Resting T cells do not contain detectable IL-2 receptor mRNA. Within 1 hour after stimulation with phytohemagglutinin (PHA), a large, presumably nuclear precursor RNA species is seen, which then gradually disappears. Mature IL-2 receptor mRNA forms appear within 8 hours after stimulation, reach peak levels between 8 and 24 hours, and then decline. Thus in PHA-activated lymphocytes the rise and fall in IL-2 receptor mRNA levels precede by more than 24 hours the peak and decline of IL-2 receptor protein expression occurring at the cell surface. Nuclease S1-protection assays indicate that IL-2 receptor mRNAs may differ in length due to the use of three different polyadenylylation signals. Further, these assays demonstrate the presence of transcripts that lack a 216-base segment within the protein-coding region and thus do not encode a functional IL-2 receptor. Nuclear transcription assays indicate that the increase in IL-2 receptor mRNA is reflected at the level of transcription. Thus, IL-2 receptor gene regulation controls IL-2 receptor expression at the cell surface and is intimately linked to the control of T-cell proliferation.
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PMID:Structure and function of the human interleukin 2 receptor gene. 288 56


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