Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adoptive immunotherapy with tumor-specific T cells has emerged as a valid approach for prevention or treatment of diseases, such as melanoma and EBV-associated lymphoma. As interleukin (IL) 15 promotes survival of CD8(+) memory CTLs, we hypothesized that it could be used to enhance antitumor immunity in vivo through the maintenance of adoptively transferred memory CTL. To test this, we treated mice bearing P1A(+) tumors with adoptively transferred T cells possessing a transgenic Valpha8(+) T-cell receptor specific for the P1A tumor antigen (called P1CTL). Mice were then randomized to receive daily low-dose IL-15 (0.5 microg/day) or PBS. Mice receiving the transgenic P1CTL and IL-15 experienced a significantly delayed tumor relapse or complete tumor regression (P < 0.002 compared with PBS), with a striking persistence of the CD8(+) Valpha8(+) P1CTL compared with mice receiving the CD8(+) Valpha8(+) P1CTL and PBS vehicle (26.3 versus 5.1% P < 10(-5)). Animals exhibiting complete tumor regression had a significant population of CD8(+) Valpha8(+) P1CTL (46%) that persisted with IL-15 treatment until 140 days after adoptive transfer and successfully defended them against tumor rechallenge without IL-15. Low-dose IL-2 afforded no protection over vehicle and resulted in lower percentages of T cells with an activated memory phenotype, lower Bcl-2 expression, and lower ex vivo antitumor cytotoxicity compared with mice treated with IL-15. Collectively, the data support the notion that exogenous low-dose IL-15 therapy can enhance and even reverse the limited efficacy of adoptively transferred tumor-specific T-cell therapy and may do so in a fashion that is superior and distinct from exogenous IL-2 therapy.
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PMID:Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2. 1552 Feb 17

Previously we reported that a mega-dose of Vitamin C enhanced the initial stage of delayed-type hypersensitivity reaction in Balb/c mice. In this study its effects were further evaluated as follows. Mice were administered Vitamin C intraperitoneally at 0.625 mg/day or at 5mg/day for variable days before, during, or after being sensitized with DNFB. T cells were isolated in each group and examined. When stimulated antigen-specifically or non-specifically in vitro, mice showed elevated thymidine uptake and a shift of cytokine secretion profiles toward Th1, i.e., elevated levels IL-2, TNF-alpha, and IFN-gamma, and lowered level of the Th2 cytokine IL-4, only when Vitamin C was administered during sensitization. T cells from those mice administered Vitamin C before sensitization or after challenge showed the same T cell properties as those from PBS-treated mice. Mice were also given 0.625 mg/day of Vitamin C during primary and/or secondary immunizations with KLH and secondary specific antibody titers in sera were measured. The total specific antibody titer was lowered in Vitamin C-treated animals whenever treatments were administered, and this was entirely attributed to decreased levels of IgG1 and IgE antibodies. Based on these results, we suggest that an exogenously administered mega-dose of Vitamin C shifts immunity in Balb/c mouse toward Th1 and that these affects occur only when Vitamin C is administered during T cell activation.
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PMID:Mega-dose Vitamin C modulates T cell functions in Balb/c mice only when administered during T cell activation. 1579 May 10

The present study describes the role of recombinant human interleukin-2 (rh IL-2) as immunomodulatory molecule in foot-and-mouth disease (FMD) vaccinal immune response in a murine model. The humoral immune response was evaluated by examining the antibody titre against FMD virus type O, A(22) and Asia 1 in serum samples obtained from different groups of mice inoculated with PBS, FMD vaccine alone; vaccine along with rh IL-2 on 0, 7, 14, 21, and 30 days post vaccination (DPV) by indirect double antibody Sandwich ELISA. The cellular immune response was also examined on different DPV by an MTT based lymphoproliferation assay in splenic mononuclear cells (SMNC) obtained from different groups. IL-2 was able to enhance the specific immune response against FMD virus type O, A(22) and Asia 1 as evident by significantly higher ELISA antibody titres (P<0.05) in serum obtained from mice receiving IL-2 along with vaccine as compared to mice immunized with vaccine alone. Similarly, the same group of mice showed significantly higher lymphoproliferative responses in SMNC against mitogen PHA and FMD virus types O, A(22) and Asia 1 on all DPVs as compared to the group inoculated with vaccine alone.
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PMID:Interleukin-2 potentiates foot-and-mouth disease vaccinal immune responses in mice. 1581 46

To investigate the antitumor immune responses induced by MAGE-3 DNA vaccine, the recombinant mammalian expression plasmid pcDNA3.1/MAGE-3 was constructed by ligating MAGE-3 gene, which was amplified by RT-PCR, and the pcD-NA3.1 + vector. The recombinant plasmids were transfected into B16 cells by liposome, the expression of MAGE-3 was checked by RT-PCR, immunocytochemistry and Western blot. Then, 100 ug recombinant plasmids were injected intramuscularly per C57BL/6 mouse on 0, 10 and 20 days, with pcDNA3.1 + plasmid and PBS as controls. Splenocytes CTLs, the level of antibodies against MAGE-3 the changes of the T lymphocyte subsets and the levels of cytokines were checked after 3 times immunization. As a result, the mice immunized with pcDNA3.1/MAGE-3 plasmid can produce MAGE-3 specific immune response. The CTLs kill activities against B16/MAGE-3 cells was 51.08 +/- 7.41%, and had significant difference (P < 0.01) compared with that of pcDNA3.1 + group (8.44 +/- 1.89%) and PBS group (5.76 +/- 1.75%). The titre of antibody against MAGE-3 was 1:15, while controls were negtive. The number of CD4 + CD8 + and the levels of IFN-gamma IL-2 increased significantly after immunization with pcDNA3.1/MAGE-3 plasmid as compared with those of control groups (P < 0.01). It is concluded that the pcDNA3.1-MAGE-3 DNA vaccine are able to induce both cellular and humoral immune responses in vivo.
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PMID:[Construction of human MAGE-3 DNA vaccine and its immune effects observed in vivo]. 1596 2

Fumaric acid derivates have been shown to stimulate T helper-2-cytokines (interleukin (IL)-4, -5) without affecting the T-helper-1-cytokine (IL-2, interferon (IFN)-gamma)-response. Herein, the influence of systemic treatment with the fumaric acid derivate dimethylfumarate (DMF) on the secretion of T helper-cytokines and the development of HSV-1 stromal keratitis (HSK) was studied in mice. The corneas from BALB/c mice were infected with 10(5) PFU of HSV-1 (KOS strain). While one group of mice was treated intraperitoneally with PBS, another group of mice received DMF at 15 mg/kg of body weight. Expression of IL-2, -4, -10 and IFN-gamma was analysed in HSV-1 activated lymphocytes by ELISA. The severity of epithelial and stromal herpetic keratitis was investigated clinically. Corneas were studied for the inflammatory cell infiltration, and the CD3-, CD4- and CD8-positive cells were analysed by immunohistochemistry. The IL-2, -4, 10 and IFN-gamma content was measured in the corneas. Virus replication in the eyes was analysed by a plaque-assay. The DTH-response, the HSV-specific T cell proliferation and the serum neutralizing antibody-titres were investigated. DMF increased IL-4 and IL-10, but not IL-2 and IFN-gamma, secretion in activated lymphocytes from the spleen. Incidence and severity of stromal HSV-1 keratitis was reduced in the DMF group (P < 0.01). In the corneas from DMF-treated mice, the numbers of CD3+ and CD4+ cells were decreased and IL-4 was increased. Severity of epithelial disease and the virus-clearance from the eyes did not differ between the PBS and DMF group of mice. DTH, HSV-specific T cell proliferation and the neutralizing antibody-titres were not impaired. DMF increased the T helper-2-cytokine secretion in activated lymphocytes. After corneal HSV-1 infection, corneas from DMF treated mice had increased IL-4 content. This is associated with an improvement of herpetic stromal keratitis and reduced corneal T cell infiltration. DMF did not impair the systemic antiviral response.
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PMID:Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T helper 2 cytokines. 1617 74

The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE66(4Glu), an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE66(4Glu). However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis.
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PMID:Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury. 1619 Nov

The fruit juice of black currant was found to contain a polysaccharide-rich substance, which was designated cassis polysaccharide (CAPS), with macrophage-stimulating activity. Especially, its interleukin (IL)-1beta-inducing activity was remarkably high, compared with other fruit juice preparations. CAPS was found to consist of rhamnose, mannose, arabinose, galactose, xylose, and glucose in a molar ratio of 11.3:0.9:54.1:29.8:2.0:1.9. CAPS turned out to be partitioned into a soluble component (CAPS-l.m.) and a precipitable component (CAPS-h.m.) with mean MWs of 80,000 and 600,000 respectively in 45% (v/v) ethanol solution. At least in vitro, CAPS-l.m. rather than CAPS-h.m. appeared to play an important role in macrophage activation. Oral administration of black currant juice and CAPS to Ehrlich carcinoma-bearing mice retarded the growth of the solid tumor by 45% and 51% respectively. CAPS administration had a stimulatory effect on the release of IL-2, IL-10, interferon-gamma, and IL-4 from splenocytes in comparison with PBS treatment in tumor-bearing mice. The IL-4 level was, however, still lower than that exhibited by a group of normal mice. CAPS showed a certain cytotoxicity directly against tumor cells.
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PMID:Immunostimulatory effects of a polysaccharide-rich substance with antitumor activity isolated from black currant (Ribes nigrum L.). 1630 83

We evaluated the usefulness of fusion vaccine prepared from IL-2-gene-transduced splenic dendritic cells (DCs) and fibrosarcoma tumor cells (QRsP) in treating of lung metastasis. The IL-2 or LacZ gene was transferred into spleen-derived DCs using an adenoviral vector. Irradiated QRsP tumor cells were fused with IL-2 gene transduced DCs (fusion/IL-2) or LacZ gene transduced DCs (fusion/LacZ) by polyethyleneglycol. These fusion cells expressed major histocompatibility complex (MHC) class I and MHC class II, CD86, CD11c and CD8alpha. IFN-gamma and cytotoxic T lymphocyte (CTL) activity of splenic lymphocytes in mice vaccinated with fusion cells increased significantly as compared with those of DC or tumor cells vaccinated mice. CTL levels in fusion/IL-2-vaccinated mice were higher than that in fusion/LacZ-vaccinated mice. The number of lung metastasis in the fusion/IL-2 or fusion/LacZ-vaccineatd mice was significantly lower than that in mice vaccinated with DCs, tumor or PBS. The introduction of the IL-2 gene into fusion cells produced more potent therapeutic effects. Our results suggest that the fusion cells prepared from IL-2 gene transduced spleen derived DCs and tumor cells have the ability to induce therapeutic effect against lung metastasis.
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PMID:[Fusion vaccine therapy by IL-2-gene-transduced dendritic cells and tumor cells]. 1631 76

Interleukin 2 (IL)-2 induces antitumor immunity and clinical responses in melanoma and renal cell carcinoma. However, IL-2 also increases the number of CD4(+)CD25(+) regulatory T (Treg) cells that suppress antitumor immune responses. The aim of the present study was to elucidate the effect of depletion of Treg cells on IL-2-induced antitumor immunity. IL-2-transfected mouse colon adenocarcinoma (MC38/IL-2) cells were implanted subcutaneously or intrahepatically into male C57BL/6 mice, and tumor growth and the proportion of tumor-infiltrating lymphocytes with Treg-cell depletion in response to treatment with anti-CD25 monoclonal antibody (PC61) were determined. In mice treated with phosphate-buffered saline, 40-60% of MC38/IL-2 tumors were rejected. In contrast, all MC38/IL-2 tumors were rejected in mice treated with PC61. The number of tumor-infiltrating CD8(+) T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4(+) and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 +/- 0.03 g, less than that in mice treated with rIL-2 (2.04 +/- 0.51 g) or PC61 alone (1.81 +/- 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg-cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8(+) T-cell population.
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PMID:Depletion of CD4+CD25+ regulatory T cells enhances interleukin-2-induced antitumor immunity in a mouse model of colon adenocarcinoma. 1727 31

The objective of this study was to assess the antiallergic effect of fermented milk prepared, respectively, with Streptococcus thermophilus MC, Lactobacillus acidophilus B, Lactobacillus bulgaricus Lb, L. bulgaricus 448, and Bifidobacterium longum B6. Female BALB/c mice fed fermented milk were immunized intraperitoneally with ovalbumin (OVA)/complete Freund's adjuvant (CFA) to evaluate the immune response by observing the secretion of cytokines IL-2, IL-4, and IFN-gamma and serum antibody IgE. The results showed that supplementation with lactic acid bacteria fermented milk did not significantly change the IL-2 spontaneous and OVA-stimulated secretions of splenocytes. However, both spontaneous and OVA-stimulated secretions of splenocytes from mice fed lactic acid bacteria fermented milk showed significantly (P < 0.05) lower levels of IL-4 (Th2 cytokine) than those from OVA/CFA-immunized mice fed non-fermented milk (OVA/CFA-milk group). The spontaneous secretion of IFN-gamma (Th1 cytokine) by splenocytes from mice fed L. bulgaricus 448 or L. bulgaricus Lb fermented milk significantly increased as compared to that from the OVA/CFA-milk group. The results showed that the ratios of IFN-gamma to IL-4 of both spontaneous and OVA-stimulated secretions in splenocytes from mice fed lactic acid bacteria fermented milk increased significantly as compared to that of PBS- or OVA/CFA-milk groups. The serum levels of OVA-specific IgE in fermented milk fed groups, especially the group fed S. thermophilus MC fermented milk, were significantly lower than those in the OVA/CFA-milk group through a 6 week feeding experiment. The results showed that milk fermented with lactic acid bacteria demonstrated in vivo antiallergic effects on OVA/CFA-immunized mice via increasing the secretion ratio of IFN-gamma/IL-4 (Th1/Th2) by splenocytes and decreasing the serum level of OVA-specific IgE.
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PMID:Antiallergic effect of milk fermented with lactic acid bacteria in a murine animal model. 1753 Aug 57


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