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)

The recognition of the monocyte/macrophage-activating properties of IL-2 has broadened our image of the biological effects of this lymphokine from those of a T cell growth factor to those of a molecule with pleiotropic effects. The detailed analysis of the mechanisms of action of IL-2 including its biological effects on different cell types and the regulation of its receptors has increased dramatically the spectrum of the biological responses that can be modified by IL-2. The regulation of the expression of the IL-2 receptor subunits differs in terms of response to extracellular stimuli and intracellular control, suggesting that the response to IL-2 will vary depending on the nature and extent of environmental stimulation. Furthermore, the fact that the IL-2R gamma chain can be part of the receptor for IL-4, IL-7, and perhaps other cytokines indicates that IL-2 may modulate the response of monocytes simply by binding or releasing the IL-2R gamma chain and thus modulating the responsiveness to IL-4 or IL-7. Conversely, the extent of utilization of IL-2R gamma chain by various cytokines may dictate the monocytic response to IL-2. In fact, the availability of IL-2R gamma chain seems to be the limiting factor in the response of monocytes to IL-2. Modulation of cytokine receptors is an integral part of the control of the IL-2 response. The induction of CSF-1 receptor by IL-2 and the positive effect of CSF-1 on the duration of the cytotoxic response in IL-2-stimulated monocytes are an interesting example of a synergistic interaction of potential physiological relevance. The response of monocytes to IL-2 can also be modulated by inhibitory circuits, such as those involving TGF-beta 1, IFN-gamma, and IL-4. However, IFN-gamma and IL-4 can also activate monocytes and the timing and relative concentrations of the various cytokines may be critical variables in determining the ultimate monocyte phenotype. These studies have given us a glimpse of a very complex picture composed of multiple backgrounds and several players. However, the present information is not sufficient to make meaningful predictions of the resulting monocyte phenotype in an inflammatory reaction in which multiple cytokines are involved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interleukin-2 and human monocyte activation. 782 65

Production of granulocyte-macrophage (GM) colony-stimulating factor by murine metastatic Lewis lung carcinoma cells (LLC-LN7) increases the number and distribution of GM progenitor cells that are suppressive to T cell responsiveness to interleukin 2 (IL-2). The presence of these GM suppressor cells can be diminished by treatment of LLC-LN7-bearing mice with low doses of 100 units IFN-gamma plus 10 units tumor necrosis factor alpha (TNF-alpha). The aim of this study was to determine whether treatment of LLC-LN7-bearing mice with IFN-gamma/TNF-alpha to diminish GM suppressor cell presence would increase the responsiveness to IL-2 immune stimulatory therapy (100-1000 IU, twice daily for 5 days). Treatment first with IFN-gamma/TNF-alpha and then also with low dose IL-2 increased both the numbers of CD4+ and CD8+ cells within the tumor and the levels of their expression of the p55 IL-2 receptor. These intratumoral T cells also had an increased cytolytic capacity toward autologous tumor cells and an increased capacity to proliferate and secrete IL-2. Such effects were observed to a lesser extent in mice that were treated with either IFN-gamma/TNF-alpha alone or with low doses of IL-2 only. The combination treatment regimen of IFN-gamma/TNF-alpha and then IL-2 was also significantly more effective at reducing the size of the primary tumor and the formation of metastatic lung nodules than were the individual treatments. These results show that treatment to minimize the presence of GM suppressor cells enhances the effectiveness of IL-2 to stimulate anti-tumor immune responses and to diminish tumor growth and metastasis.
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PMID:Treating tumor-bearing mice with low-dose gamma-interferon plus tumor necrosis factor alpha to diminish immune suppressive granulocyte-macrophage progenitor cells increases responsiveness to interleukin 2 immunotherapy. 785 Aug 4

In a previous study, we observed that a cell-free Salmonella typhimurium extract induced suppression of mitogen-induced T-cell proliferation and that this suppression involved nonresponsiveness of T-cells to interleukin-2 (IL-2) and augmentation of IL-2 receptor (IL-2R) expression. In this study, we found that inhibition of phytohemagglutinin (PHA)-stimulated murine spleen cell proliferation induced by a cell-free S. typhimurium extract was reversed by treatment with an anti-interferon-gamma monoclonal antibody (anti-IFN-gamma Ab), but not by interleukin-4 or NG-monomethyl-L-arginine, which is known to inhibit nitric oxide (NO)-secretion from spleen cells in culture. However, IL-2R expression was augmented by treatment with the extract, although this was independent of an NO-mediated mechanism. Only anti-IFN-gamma Ab treatment reduced the augmented IL-2R expression to a normal level. These results suggest that the suppression of T-cell proliferation induced by the Salmonella cell-free extract is associated with augmentation of IL-2R expression in an NO production-independent manner.
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PMID:Inhibition of T-cell proliferation induced by a cell-free Salmonella typhimurium extract does not involve a nitric oxide-mediated mechanism. 789 93

Glutamine is required for the proliferation of lymphocytes, but quantitative effects on discrete steps of activation remain unknown to date. Therefore the influence of glutamine (range: 0 mM-1 mM) on the in vitro response of human peripheral blood mononuclear cells (PBMC) to a mitogenic anti-CD3 monoclonal antibody (mAb) was investigated. Expression of surface activation markers by flow cytometry, presence of mRNA of cytokine genes by polymerase chain reaction, release of cytokines by ELISA, and entering into the cell cycle by flow cytometry were sequentially analyzed. Proliferation was measured by a 3H-thymidine incorporation assay. mRNA coding for IL-2, IL-2 receptor, IL-4, IL-5, GM-CSF, and IFN-gamma was detectable independently from exogenous glutamine provision; expression of the cell surface activation marker CD69 was also glutamine independent. In contrast, later activation events including the expression of the surface activation markers CD25, CD45RO, and CD71 as well as the production of IFN-gamma were found to require exogenous glutamine supply. In contrast, production of TNF-alpha could be observed in the absence of glutamine and was increased to a limited extent by exogenous glutamine. The overall lymphocyte response as reflected by entering into the cell cycle and proliferation was directly correlated with the glutamine concentration of the culture medium. Efficient progression through the cell cycle was found to require at least 0.5 mM glutamine and an increase in glutamine concentration from 0.1 mM to 1 mM enhanced proliferation by 50%. These results were supported by data obtained following anti-CD3 stimulation of a CD4+ T cell clone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exogenous glutamine requirement is confined to late events of T cell activation. 790 86

Changes in lymphocyte traffic in efferent lymph from the prescapular lymph node of sheep were monitored during local primary and secondary infection with blowfly, Lucilia cuprina. During primary infections the response was characterised by an increase in the output of CD4+ T cells over CD8+ T cells for the first 48 h after wound initiation. By 72 h the output of CD8+ T cells exceeded that of CD4+ T cells. During secondary infections the increased output of CD8+ T cells was more pronounced and occurred earlier at approximately 48 h. The percentage of B lymphocytes as measured by sIg, CD45R and MHC class II expression increased at approximately 96-120 h after both primary and secondary infections, with the secondary response being greater than the primary. This increase in B cells corresponded with peak antibody titres recorded in the efferent lymph to a first instar antigen preparation as measured by ELISA. An increase in IFN-gamma and soluble IL-2 receptor was recorded after both primary and secondary infections, with the response after secondary infection being greater than that recorded after primary larval infections.
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PMID:The immune response of sheep infected with larvae of the sheep blowfly Lucilia cuprina monitored via efferent lymph. 791 82

Immunohistochemical and immunoserological evidence supports the involvement of both cell-mediated and humoral mechanisms in the pathogenesis of melanocyte destruction in vitiligo. Punch biopsies from depigmented vitiliginous skin (VS), normal-looking pigmented skin (PS), and marginal skin (MS) from patients with generalized vitiligo (n = 15) were labeled with K 1.2.58, OKM1 (CD11b), Leu 11b (CD16), Leu 19 (CD56), IFN-gamma receptor, IL-2 receptor (CD25), IgG, IgM, C3c, and C3d MoAbs. In addition, in vitro effects of vitiligo sera (n = 13) on human newborn melanocytes (HMel) under different culture conditions were studied. The immunohistochemical findings showed absence of K 1.2.58+ epidermal melanocytes in VS and abnormal morphology in MS. In these areas, a few CD11b+ cells in the dermis and epidermis could be detected but no significant numbers of CD16+ or CD56+ cells were seen among the mononuclear cellular infiltrate. IL-2 and IFN-gamma receptors were clearly expressed by the cellular infiltrate. No significant deposition of complement or immunoglobulin was seen. The addition of vitiligo sera to HMel cultures induced a significant cellular proliferation. The stimulation of cell proliferation occurred regardless whether the sera were added alone or when preheated (56 degrees C for 1 hr) and then supplemented with a complement source (P < 0.01 at 2%, P < 0.001 at 10%, and P < 0.01 at 20% for sera alone) (P > 0.05 at 2%, P < 0.05 at 10%, and P < 0.01 at 20% for decomplemented sera plus complement).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Further evidence for involvement of both cell mediated and humoral immunity in generalized vitiligo. 807 43

Ling Zhi-8 (LZ-8) is a protein purified from Ganoderma lucidium, a Chinese medicinal fungus thought to possess potent effects on the immune system. When examined for its effects on lymphocytes, LZ-8 exhibited potent mitogenic effects on human peripheral blood lymphocytes (PBL), inducing a bell-shaped dose-response curve similar to that caused by PHA and other lectin mitogens. Fractionation experiments indicated that the proliferative response in the PBL cultures was primarily due to T cells, but was monocyte dependent. Stimulation of PBL with LZ-8 resulted in the production of IL-2 and a corresponding upregulation of IL-2 receptor expression. In addition to T cell proliferation, microscopic examination of LZ-8-stimulated PBL revealed that LZ-8 induced cellular aggregate formation. The aggregate formation correlated with a dramatic rise in ICAM-1 expression and an increased production of IFN-gamma, TNF alpha, and IL-1 beta, molecules associated with regulation of ICAM-1 expression. Both the aggregate formation and the proliferative effects of LZ-8 were blocked by addition of monoclonal antibody to either CD18 or CD11a, the counterreceptor complex components for ICAM-1. Furthermore, addition of neutralizing antibodies to both IL-2 receptor and TNF alpha blocked aggregate formation, cellular proliferation, and ICAM-1 expression. These findings demonstrate that LZ-8 is a potent T cell activator, mediating its effects via cytokine regulation of integrin expression.
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PMID:Ling Zhi-8: a novel T cell mitogen induces cytokine production and upregulation of ICAM-1 expression. 810 83

The mechanisms whereby anti-CD4 monoclonal antibodies can block human peripheral blood lymphocyte response to staphylococcal enterotoxin B (SEB) were investigated. Preincubation of peripheral blood mononuclear cells (PBMC) with anti-CD4 mAbs resulted in a profound inhibition of SEB-induced DNA synthesis, while simultaneous addition of antibody and superantigen did not reproducibly decrease the proliferative response. Inhibition was achieved at a very low antibody concentration (0.1 microgram/ml). It was not increased by cross-linking of anti-CD4 mAb nor mediated by Fc-dependent signals as F(ab')2 antibody fragments were as effective as intact antibodies. Inhibition of proliferation was associated with a profound diminution of IL-2 and IFN-gamma secretion, CD25 (the alpha chain of IL-2 receptor) expression, and blast transformation. Stimulation by SEB after prior ligation of surface CD4 proteins by antibodies was associated with an increased percentage of lymphocytes with chromatin condensation and nuclear fragmentation. It was concluded that stimulation of mature peripheral T cells by SEB through T cell receptors induces an apoptotic signal providing that a small proportion of surface CD4 molecules has interacted with antibodies or F(ab')2 fragments before stimulation by SEB, while simultaneous addition of SEB and anti-CD4 mAb does not prevent the development of a complete activation program in this system. Possible implications of these observations regarding selective clonal deletion of autoreactive T cells by administration of anti-CD4 mAbs in patients with auto-immune diseases are discussed.
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PMID:Inhibition of human T cell response to staphylococcal enterotoxin B by prior ligation of surface CD4 molecules. 810 87

We have studied the effects of human rIL-12 on the proliferation and generation of cytotoxic activity in human CTL precursors. Purified human blood CD8+ T lymphocytes were stimulated overnight with immobilized alpha-CD3 and cultured 3 to 4 additional days under various conditions. The addition of IL-12 resulted in a marked (10- to 20-fold), dose-dependent, augmentation of cytotoxicity per cell with a smaller (2-fold) increase in cell number. IL-12 augmentation of proliferation and cytotoxicity of CD8+ T cells was not inhibited by a mAb to the p55 subunit of the IL-2 receptor (alpha-Tac) at a concentration sufficient to block the activity of exogenously added IL-2, indicating that the activity of IL-12 did not require IL-2. Addition of IL-12 at the time of alpha-CD3 activation or 1 day later was highly effective at augmenting cytotoxicity, whereas delayed addition of IL-12 (day 2 or 3) resulted in a smaller increase in CTL activity with no increase in cell number. IL-12 at all doses tested synergized with low dose IL-2 in inducing the proliferation and differentiation of CD8+ T cells. The synergistic effect was not blocked by adding neutralizing serum to IFN-gamma. In contrast to this synergistic effect, IL-12 significantly inhibited the proliferation observed in the presence of higher concentrations of IL-2 (4,500 and 13,500 pg/ml). An inhibitory effect of IL-12 was also observed when IL-12 was added to CD8+ T lymphocytes 3 days subsequent to activation with alpha-CD3 and IL-2. This broad set of potent effects of IL-12 on CD8+ T cell responses suggests that IL-12 may play an important immunoregulatory role on CTL development in vivo and may be a useful tool for manipulating this process in vivo for investigational and immunotherapeutic purposes.
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PMID:Effects of IL-12 on the generation of cytotoxic activity in human CD8+ T lymphocytes. 810 66

Type I, insulin-dependent diabetes (IDD) in both man and animals results from a specific autoimmune destruction of the pancreatic beta cells involving both humoral and cellular immune mechanisms. The pathognomonic histologic lesion, termed insulitis, is an inflammatory and immune cell infiltrate of the pancreatic islet cells. While recent histological and flow cytometric analyses have identified the cell composition of the infiltrate, the presence of a cell population may not reflect the functional reactivities important for beta cell destruction. In the present study, we have investigated the possible functional reactivities of islet-infiltrating mononuclear cell populations by measuring increased cytokine mRNA usage. Results indicate that 1) cytokine mRNA profiles exhibited by islet-infiltrating cells of female and male NOD mice were quite similar with the exception of IL-6 expression and the marked differences in the levels of IL-2 receptor and IL-1 alpha mRNA, 2) CD4+ T lymphocytes expressed IL-4, presumably IL-5, and occasionally IL-10 mRNA but no detectable IL-2 mRNA, 3) CD8+ T lymphocytes exhibited TNF-beta, perforin and high levels of IFN-gamma, and 4) IL-7 was expressed in the islet at very high levels. These findings, together with our earlier flow cytometric analyses of the islet-infiltrating cells, have permitted construction of a detailed model for the natural history of autoimmune diabetes. Interestingly, this model, based on a TH2- and not a TH1-mediated scheme, questions the more popular concepts currently thought to form the bases of the autoimmune reactions underlying IDD.
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PMID:Insulin-dependent diabetes in the NOD mouse model. II. Beta cell destruction in autoimmune diabetes is a TH2 and not a TH1 mediated event. 810 89

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