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)

A possible correlation between the pathogenicity of autoimmune T cells and their lymphokine production, expression of functional adhesion molecules and expression of some surface antigens was examined. We used four retinal antigen-specific Lewis rat T cell lines and sublines: one specific to the major pathogenic epitope of the human retinal soluble antigen (S-Ag; residues 337-356), and three specific to the major pathogenic epitope of the bovine interphotoreceptor retinoid binding protein (IRBP; residues 1177-1191). The lines have different degrees of uveitogenicity, from highly pathogenic to nonpathogenic. All four T cell lines produced roughly equivalent amounts of interferon-gamma, lymphotoxin/tumor necrosis factor (TNF alpha/beta), interleukin-3, interleukin-6 and transforming growth factor-beta. Interleukin-4 activity could not be detected. The lines also expressed similar levels of functional adhesion molecules, as measured by binding to cultured rat aorta endothelial cells. The nonpathogenic subline, however, was the lowest responder to antigenic stimulation with respect to proliferation and interleukin-2 production. Examination of cell surface antigens showed that in contrast to the other lines, the majority of cells in the nonpathogenic subline lacked detectable expression of CD4. No difference was found in the level of expression of the IL-2 receptor and T cell antigen receptor among the four lines. Because CD4 is the restricting element in these lines, reduced CD4 expression in the nonpathogenic subline may at least partially explain its poor response in vitro to antigenic stimulation. All three attributes could be connected to lack of pathogenicity of this line in vivo. These results support the contention that class II-restricted recognition of autoantigen within the neuroretina by uveitogenic T lymphocytes must occur as an initial step in the pathogenesis of EAU. A defect in this step will preclude pathogenesis regardless of some other functional attributes possessed by effector T cells, such as production of inflammatory lymphokines and expression of adhesion molecules.
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PMID:Uveitogenic T lymphocytes in the rat: pathogenicity vs. lymphokine production, adhesion molecules and surface antigen expression. 752 41

Renal biopsies were performed 1 week following renal transplantation at a time without clinical evidence of rejection in 43 patients (13 females, mean age 48 years range 18-60 and 30 males, mean age 43 years range 17-59 years). Thirty-six biopsies were available for histological or immunohistochemical analysis. Immunohistochemical analyses were performed with monoclonal antibodies against leukocytes (CD45), monocytes (WT14), complement factor 3 (C3), T-cells (Leu4), T-cell receptor alpha beta and gamma delta, tumour necrosis factor alpha (TNF alpha), IL-2 receptor (IL2-R, TAC), intercellular adhesion molecule-1 (ICAM1) and HLA-DR. The slides were scored semiquantitatively with the observers having no knowledge of clinical or patient data. TNF alpha and IL-2R were also measured by quantative PCR. None of the studied parameters correlated to delayed graft function or graft loss. Histological analysis showed that both focal interstitial infiltrate (18/35) and tubular basement membrane disruption (11/35) were followed by a higher incidence of subsequent rejection (P = 0.03 and 0.02 respectively). Also positivity for WT14 around tubuli (P = 0.02) was associated with subsequent occurrence of rejection. The intensity of staining of ICAM-1 on PTC as well as TAC on proximal tubular cells was associated with the number of subsequent rejection episodes. The association between the IL-2 receptor and subsequent rejection was also found applying PCR to the tissue specimens. We conclude that the presence of focal interstitial infiltrates and tubulitis in 1-week biopsies from well-functioning grafts carries an increased risk of subsequent rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation by histology, immunohistology and PCR of protocollized renal biopsies 1 week post-transplant in relation to subsequent rejection episodes. 756 15

The cytokine profiles produced by peripheral blood mononuclear cell (PBMC) cultures were dependent upon the nature of the stimulus used. Powerful lymphocyte activators such as mitogens induced rapid cell proliferation together with the production of both inflammatory (IL-1 alpha, IL-1 beta, IL-6 and TNF alpha) and immune (IFN-gamma, TNF-alpha and TNF-beta) cytokines, and immune activation markers (soluble IL-2 receptor, neopterin and xanthopterin). Bacterial endotoxin failed to induce cell proliferation but resulted in the rapid production of inflammatory cytokines together with a short burst of IFN-gamma production, without the production of the other immune cytokines or activation markers. Alloantigen stimulation gave a typical immune cytokine and marker profile, with little or no production of inflammatory cytokines. Re-call antigens (candida and PPD) induced maximal cell proliferation at days 5 to 6, but induced little or no production of inflammatory cytokines. Markedly different immune cytokine profiles were obtained with these re-call antigens. Candida induced an early burst of IFN-gamma production on day 1 followed by later production of TNF-alpha. In cultures stimulated with PPD, both IFN-gamma and TNF-alpha were detected from day 2. With both re-call antigens, the levels of production of the activation markers were equivalent to the proliferative responses obtained.
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PMID:Stimulus-dependent production of cytokines and pterins by peripheral blood mononuclear cells. 762 84

We previously demonstrated the potential of anti-IL-2R and anti-TNF alpha moAbs in the treatment of acute graft-versus-host disease (GVHD). However, one major problem was the recurrence of acute GVHD on treatment discontinuation. To target the two main effectors of acute GVHD lesions, T and NK cells on the one hand and TNF alpha on the other, we combined anti-CD2 and anti-TNF alpha moAbs. Then to prevent acute GVHD recurrence, we administered anti-IL-2R moAbs known for their inhibitory effect on activated cells. We included 15 patients with steroid-resistant acute GVHD. Seven were grafted from a genotypically-identical sibling, 5 from HLA-matched unrelated donors and 3 from partially-matched related donor. Prophylaxis of acute GVHD consisted of cyclosporin A +/- methotrexate or corticosteroids. Before treatment 6 patients had grade II, 2 patients grade III and 7 patients grade IV acute GVHD. Anti-TNF alpha (B-C7) moAbs (10 mg/day/4 days) were combined with anti-CD2 (B-E2) moAbs (10 mg/day/10 days) on the fifth day (day 5), anti-IL-2 receptor (B-B10) moAbs were given at 10 mg/day/10 days followed by 5 mg every other day for another 50 days. On day 15, 5 patients achieved a complete remission, 4 a very good partial response (62% a good response), 2 had a partial response and 4 did not respond. GVHD recurred in 4 of the 9 responders, although anti-IL-2R moAb treatment was maintained. Three patients are long-term survivors without chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients. 767 Mar 94

Pregnancy is associated with modifications in the maternal immune system that may be involved in the absence of rejection of the fetoplacental graft characterized by the presence of paternal antigens. This active and specific tolerance towards the fetoplacental unit seems to be compromised in pregnancy-induced hypertension (PIH). To evaluate whether the immunological state in patients with PIH is altered with respect to normal pregnant women we studied 15 patients with PIH, 15 uncomplicated pregnant and 10 healthy nonpregnant women using monoclonal antibodies directed to specific lymphocyte antigen determinants, cytokines (TNF) and soluble molecules (sIL-2R, sCD8). The percentage of CD4 lymphocytes and of natural killer (NK) cells was significantly higher in PIH patients compared to controls (CD4: 42.9 +/- 10.5 vs. 32.7 +/- 12.5%; p < 0.05; NK: 14.7 +/- 6.3 vs. 8.3 +/- 3.4%; p < 0.01). However, these values did not differ when compared to normotensive nonpregnant controls (CD4: 53.1 +/- 5.9%; NK: 17.2 +/- 7.1%). In addition, the soluble IL-2 receptor (sIL-2R) was higher in PIH patients when compared to control patients (725.5 +/- 194.2 vs. 482.5 +/- 187.2 U/ml; p < 0.01). The immune response observed in normal pregnancies responsible for the tolerance towards the fetoplacental unit seems to be altered in PIH patients as suggested by higher levels of CD4 and NK cells, and sIL-2R. This may lead to a chronic rejection syndrome and be involved in the pathophysiology of PIH.
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PMID:Cell-mediated immunity imbalance in pregnancy-induced hypertension. 785 7

Cytokine gene expression was determined in vivo in the lungs and spleens of Mycoplasma pneumoniae-infected BALB/c mice by means of qualitative and semiquantitative PCR-mediated mRNA amplification. During the acute phase of both primary and secondary infections, cytokines commonly associated with innate resistance, TNF alpha, IFN gamma, IL-1 beta and IL-6, were expressed. In contrast, early expression of the genes for IL-2 and IL-2 receptor was detected only during reinfection. Expression was greater in the lungs than in the spleen, attesting to the rapid accumulation of lymphocytes at the infected site. Interestingly, IL-2 mRNA expression declined rapidly and was no longer detectable after 24 h, whereas IL-10 mRNA levels rose sharply during the same period. During reinfection, mRNAs for TNF alpha and IL-6 were 10-fold and for IFN gamma about 50-fold higher than during primary challenge. The results suggest that the pathogenesis of M. pneumoniae diseases may be associated with elevated expression of proinflammatory cytokines.
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PMID:Cytokine gene expression in the lungs of BALB/c mice during primary and secondary intranasal infection with Mycoplasma pneumoniae. 792 Dec 54

High levels of the macrophage activation marker neopterin have been described in metastatic cancer patients. Since macrophages may either counteract or stimulate tumor development, it is important to establish which macrophage activity is mainly related to neopterin release. The present study was carried out to evaluate neopterin levels in metastatic solid tumor patients in respect with the antitumor macrophage cytokine TNF and with soluble IL-2 receptor (SIL-2R), whose secretion is stimulated by macrophages and it is associated with the immunosuppressive status of cancer patients. The study included 35 patients with metastatic solid neoplasms. Serum levels of neopterin, TNF and SIL-2R were measured in blood samples collected during the morning. Abnormally high concentrations of neopterin were seen in 18/35 (51%) patients. Patients with high levels of neopterin showed significantly higher concentrations of SIL-2R than those with normal neopterin values, whereas no difference was found in TNF levels. This study would suggest that the increased secretion of neopterin may reflect macrophage-mediated immunosuppression in metastatic solid neoplasms, rather than to be associated with the antitumor activity of macrophages.
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PMID:A study of interactions among markers of macrophage functions in metastatic solid tumors: neopterin levels in relation to those of tumor necrosis factor-alpha and of soluble interleukin-2 receptors. 797 92

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

Data from a variety of sources suggest that one target cell for levamisole might be the macrophage. Current results reveal that oral levamisole pre-treatment provides elicited peritoneal macrophages with the ability to respond better to ex vivo LPS stimulation, and that levamisole can directly act on LPS-stimulated macrophages in vitro, resulting in enhanced production of IL-1, a key mediator of the immune response. These data offer further biological and immunologic evidence that IL-1 production is indeed enhanced by levamisole. Finally, these phenomena were not confined to macrophages taken from mice given levamisole. Increased IL-1 expression was found to occur for cells treated in vitro with levamisole, demonstrating that there were direct effects by levamisole on LPS-stimulated macrophage cytokine production. IL-1 has been reported to have a number of direct and indirect anti-tumor effects which might be sufficient to provide localized protection against tumor invasion or growth in the adjuvant setting. The findings described above are therefore consistent with suggestions of an increased host response in certain types of cancer due to levamisole treatment, and are also consistent with reports of levamisole's providing a beneficial effect in other cases of immunodeficiency disease. Recent clinical data provided by Janik et al. demonstrate that levamisole administration caused increases in circulating levels of neopterin and soluble IL-2 receptor (sIL-2R). This in vivo result is consistent with in vitro data showing augmented IL-1 induction after levamisole treatment, since neopterin is a marker for macrophage activation and sIL-2R release correlates with IL-2 production and binding after IL-1 activation of T-cells. These data are therefore consistent with the hypothesis that levamisole can induce a macrophage-derived cytokine cascade which may have beneficial effects in host responses to human cancer. It is attractive to speculate that there may be increased cytokine expression in vivo (yet to be confirmed) which might contribute to the added clinical benefit when 5-FU is combined with levamisole. Data from nude mice bearing human tumor xenografts demonstrate improved antitumor responses to 5-FU in combination with levamisole, and it will be interesting to determine whether increased interferon, TNF, or other cytokines can be observed in this model. In addition, the ability of levamisole to increase ICAM-1 expression on certain tumor cell lines may be a mechanism by which similar cells are rendered more sensitive to host effector mechanisms in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Experimental modulation of IL-1 production and cell surface molecule expression by levamisole. 810 13

The aim of this study was to investigate the augmentative effect of a streptococcal preparation, OK432, on the immunological competence of hepatic macrophages. We found that OK432 was distributed predominantly to hepatic macrophages after intravenous injection, and Northern blot analysis revealed that OK432 induced the gene expression of IL-1 alpha, beta, and TNF alpha in the liver. The induction of mRNAs was evident 1 h after the intravenous injection of OK432 and their accumulation reached a maximal level at 3 h. TNF production of hepatic macrophages was also increased by the intravenous injection of OK432. Furthermore, OK432 significantly increased the proportion of IL-2 receptor-positive hepatic macrophages. As for antitumor activity in the liver being augmented by OK432, the cytotoxic and cytostatic activity of hepatic macrophages from OK432-treated rats against tumor cells was significantly increased and OK432 markedly reduced the number of tumor nodules in the liver after the inoculation of tumor cells via the portal vein. These findings, which indicate that OK432 has various immuno-stimulating actions on hepatic macrophages, leading to the augmentation of antitumor activity in the liver, suggest that OK432 may be of some benefit in helping to prevent hepatic metastasis, at least in part, via its activation of hepatic macrophages.
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PMID:Augmented local immunity in the liver by a streptococcal preparation, OK432, related to antitumor activity of hepatic macrophages. 820 52

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