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)

In the present study, we have compared the T cell antigenic determinants on nucleoprotein (NP) of influenza A/NT/60/68 virus recognized by BALB/c mice (H-2d) after vaccination using several different vehicles with the determinants recognized after exposure to infectious virus. Mice were immunized s.c. with: 1) purified recombinant NP with three different adjuvants--alum, saponin, or CFA; 2) whole inactivated A/Okuda virus in PBS or saponin; or 3) live attenuated Salmonella typhimurium AroA- vector expressing NP. A series of overlapping synthetic peptides that cover more than 90% of the amino acid sequence of NP were used to map the Th cell epitopes. The results showed that the same limited number of major epitopes were recognized after each of the different immunization regimes. Secondary in vivo boosting using the same vehicles as for the primary immunization did not increase the number of different T cell sites recognized. The T cell responses after intranasal infection with infectious A/NT/60/68 or A/PR/8/34 virus also showed a similar pattern of recognition of the major CD4-positive T cell epitopes. The only exception was that the region corresponding to residues 401-419 was only recognized after exposure to NP from A/NT/60/68 but not A/PR/8/34. This is probably because the two viruses differ in amino acid sequence at positions 408 and 411 within this part of the NP molecule. In contrast to the results observed with CD4-positive T cell epitopes, the major determinant recognized by CD8-positive T cells was only presented after live viral infection. The results in this study have important implications for vaccine design, inasmuch as they indicate that the same dominant CD4 T cell determinants on NP presented by vaccination with NP are also recognized by T cells from mice exposed to infectious virus.
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PMID:Selection of the same major T cell determinants of influenza nucleoprotein after vaccination or exposure to infectious virus. 171 66

The placenta is a rich source of immunocompetent cells. We have studied the phenotype, number and origin of placental mononuclear blood cells isolated from 32 normal term placentae using 4 color flow cytometry. Respective maternal and cord blood leucocyte preparations were also compared. Placental tissue without extraembryonic membranes was cut into small pieces and divided. One portion was washed extensively with ice-cold PBS. Both tissue portions were disrupted in a blender and cells were dissociated by using a 180 mu sieve. Leucocytes were isolated by Ficoll-Hypaque density gradient centrifugation. Maternal and cord bloods were HLA typed and in cases of HLA-A2 or B7/40 disparity, monoclonal anti-HLA antibodies to these antigens showed that unwashed placental tissue contained 35% maternal and 65% fetal cells. This ratio, however, was not reflected for a given cell phenotype. In comparison, washed placental tissue contained cells of fetal origin only. Both unwashed and washed placental tissue contained fewer CD3 and CD4, but more CD8 cells than maternal and cord blood. Markers of NK cells such as, CD16, CD56, and CD57 showed this cellular phenotype to be 15 times more abundant in the placental preparations than in cord and maternal blood. The quantitative differences between peripheral blood and placental CD8 and NK cells were further explored with an antiprogesterone receptor antibody in combination with anti-CD8, anti-CD57 and anti-HLA-DR. The number of progesterone receptor (PGR) positive cells was three times higher in placental tissues than in cord or maternal blood. These data indicate that the phenotypic frequencies of certain placental leucocytes are significantly different from maternal and fetal peripheral blood. Progesterone and the presence of PGR may be important in the differential retention of placental leucocytes.
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PMID:Phenotypic characterization of normal human placental mononuclear cells. 827 Dec 37

Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8+ and CD4+ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8+ cells act in both anti- and pro-inflammatory capacities, suggesting that functionally distinct CD8+ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8+ lymphocytes, had no effect on HgCl2-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl2-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann-Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-gamma), suggesting that CD8+ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8+ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.
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PMID:Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity. 891 74

Age-related decline of the thymus in ICR female mice was studied following long-term (three month) weekly exposure to hydrocortisone acetate. When examined one week after cortisone injections, the well-known thymic atrophy was observed. Five weeks after 12 hydrocortisone injections, the cortical volume fraction (Vc), cortical/medullary ratio (C/M), the number of thymocytes and CD4/CD8 profiles were in the range that characterizes younger mice, compared with PBS-injected mice, uninjected controls, or mice given a single hydrocortisone injection 5 weeks earlier. It seems as if thymic involution with age was suspended during the period of glucocorticoid exposure.
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PMID:Thymic aging in ICR female mice is suspended by prolonged hydrocortisone exposure. 936 36

Monocytes and macrophages mediate cytotoxicity after appropriate activation and thus represent effectors secondary to T lymphocytes and natural killer (NK) cells. However, very little is known about the role of activated monocytes in organ allograft rejection. In this study, isogeneic (LEW to LEW) and fully allogeneic (DA to LEW) rat kidneys were grafted to bilaterally nephrectomized recipients. Four days after transplantation a comprehensive sample of leucocytes was recovered by perfusion of the recipients' vasculature with phosphate-buffered saline containing EDTA (PBS/EDTA). Monocytes were enriched by density gradient centrifugation and their physical parameters and immunophenotype were investigated by flow cytometry in comparison with untreated, specified pathogen-free (SPF) LEW rats. Isotransplantation and allotransplantation of kidneys dramatically increased the absolute number of intravascular monocytes in the recipient. Analysis of NKR-P1 (CD161), CD4, CD62L, CD43, CD11a, CD18 and MHC class II expression identified at least two monocyte populations in all experimental groups. In graft recipients it was evident that activated monocytes were able to express and upregulate NKR-P1 and CD8, which have not been detected in these cells to date. If activated monocytes utilize NKR-P1 and CD8, by analogy to NK cells and lymphocytes these cells may be endowed with additional pathways to upregulate cytolytic functions and effect allograft damage.
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PMID:Phenotype of rat monocytes during acute kidney allograft rejection: increased expression of NKR-P1 and reduction of CD43. 960 Mar 14

In in vivo tolerance induction, the dose of tolerogen injected is generally linearly correlated to the length of tolerance induced. Small, medium and large doses are related to no, partial and long-term tolerance, respectively. However, even with injection of substantially large doses of tolerogen, the length of tolerance induced varies over a wide range. Most of the recipients can still reject donor grafts. In this study, it is shown that the linear dose-response can be altered into an all or nothing response in a H-Y antigen-specific TCR transgenic (Tg) mouse model. In thymectomized female Tg mice, injection of 3, 30 and 100 x 10(6) male spleen cells was correlated to no, partial and massive deletion of Tg (alpha T beta T) CD8 cells, respectively. When the thymectomized Tg mice were injected with 9 x 10(6) T cell-enriched (T+) male cells, one half of the recipients showed no deletion of alpha T beta T cells, and in the other half massive deletion occurred. In complete correlation with deletion, all male skin grafts were rejected in the undeleted group as PBS-injected controls, whereas with massive deletion they were indefinitely tolerized. Thus, partial deletion and partial tolerance can be avoided. Injection of 18 x 10(6) male T+ cells induced long-term tolerance in all the recipients. The all or none T cell deletion and long-term tolerance induction has not only significant implications in understanding the mechanism of peripheral tolerance induction, but also in tolerance induction in transplantation, gene therapy and the prevention and treatment of autoimmune diseases.
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PMID:All or none peripheral tolerance induction in H-Y antigen-specific TCR transgenic mice. 977 95

T cell cytokine profiles in the spleens and Porphyromonas gingivalis-induced lesions of P. gingivalis-immunized mice were examined. BALB/c mice were immunized with P. gingivalis outer membrane (OM) antigens/mouse weekly for 3 weeks followed by challenge with live organisms 2 weeks after the final immunization. Control mice were immunized with PBS. Spleens were excised at 0 and 4 days and lesions at 1, 4, and 7 days after challenge. Splenic and lesional CD4 and CD8 cells were stained for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma, and IL-10. More than 50% of the T cells in the spleens of immunized mice were IFN-gamma positive at day 0 which was significantly higher than for IL-4 or IL-10, these levels decreasing significantly 4 days after challenge. Less than 6% of the T cells in sham immunized mice were cytokine positive at day 0, although at day 4, there was a significant increase in the percent IL-10 positive CD4 cells and IL-4 and IL-10 positive CD8 cells. There were no differences in the percent IL-4, IFN-gamma, or IL-10 positive T cells in the lesions of immunized mice, but there was a dramatic decrease at day 7 to very low levels in control mice. In conclusion, the results of the present study show a predominant Th1 response in the spleens of BALB/c mice after immunization with P. gingivalis OM antigens, suggesting that a protective immune response to P. gingivalis may involve a strong IFN-gamma response.
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PMID:Cytokine profiles of lesional and splenic T cells in Porphyromonas gingivalis infection in a murine model. 980 13

Thymic atrophy is a prominent feature of malnutrition. Forty-eight hours' starvation of normal mice reduced the total thymocyte count to 13% of that observed in freely fed controls, predominantly because of a diminution in the cortical CD4(+)CD8(+) thymocyte subpopulation. Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes. The ob/ob mouse, which is unable to produce functional leptin because of a mutation in the obese gene, has impaired cellular immunity together with a marked reduction in the size and cellularity of the thymus. We found that ob/ob mice had a high level of thymocyte apoptosis resulting in a ratio of CD4(+)CD8(+) (cortical) to CD4(-)CD8(-) (precursor) thymocytes that was 4-fold lower than that observed in wild-type mice. Peripheral administration of recombinant leptin to ob/ob mice reduced thymocyte apoptosis and substantially increased both thymic cellularity and the CD4(+)CD8(+)/CD4(-)CD8(-) ratio. In contrast, a comparable weight loss in pair-fed PBS-treated ob/ob mice had no impact on thymocyte number. In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy.
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PMID:Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. 1052 43

To examine the direct effects of IL-4 on peripheral nervous system (PNS) we injected recombinant rat IL-4 (rrIL-4) into the sciatic nerve of normal adult Lewis rats. Histopathological and immunohistochemical observations revealed that 1 day after injection, a large number of macrophages and MHC class II-positive cells appeared within both the perineurium and endoneurium. Only few CD4(+)and CD8(+)T cells existed in the endoneurium. From day 4 to day 7, we observed a gradual decline of inflammation, but the number of infiltrates in rrIL-4 injected nerves was significantly higher compared with sterile PBS-injected control group. On the contrary, demyelination affected significantly fewer nerve fibres in the rrIL-4-injected nerves compared with control group on day 7. Intraneural injection of rrIL-4 results in high grade inflammation and mild demyelination in the PNS.
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PMID:High inflammation and mild demyelination in the peripheral nervous system induced by an intraneural injection of RR interleukin-4. 1084 69

To increase the antitumor effects of cytosine deaminase (AdCD) gene therapy and induce more potent antitumor immunity, Th1 cytokine interleukin-18 encoded adenovirus (AdIL18) was combined with adenovirus encoding CD (AdCD) for the therapy of established murine B16 melanoma. Combination therapy of the tumor-bearing mice with AdIL 18 and AdCD/5FC inhibited the growth of the subcutaneous B16 tumors more significantly, compared with AdIL 18 or AdCD/5FC alone. In vivo depletion analysis with anti-CD4, anti-CD8 or anti-NK 1.1 McAb illustrated that both CD8+ T cells and CD4+ T cells played key roles in the augmented antitumor response of the combined therapy. Peptide/MHC tetramer represents a powerful and general tool for rapid, highly sensitive, and direct analysis of antigen-specific T cells. In this study, we prepared H-2Kb/TRP-2180-188 tetramer, which was demonstrated to bind H-2Kb-restricted, B16 melanoma-specific CD8+ T cells. B16 specific H-2Kb/TRP2180-188 tetramer was used to stain the tumor-specific CD8+ T cells and the results showed that CD8+ tetramer+ T cells were about 3-5% of the splenic CD8+ T cells derived from tumor-bearing mice after combined therapy. The CTL cytotoxicity was markedly induced in mice after combined therapy, suggesting efficient induction of tumor-specific CD8+ T cells after combined gene therapy with AdCD/5FC/AdIL18. IL-18 gene transfer could significantly augment the cytotoxicity of NK cells and macrophages, and increase the production of interleukin-2 and interferon-gamma, as compared with treatments with AdCD/5FC, AdlacZ/5FC or PBS. These data suggested that in vivo IL-18 gene transfer could augment the antitumor effects of CD suicide gene therapy through efficient induction of antitumor immunity.
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PMID:Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity. 1108 76


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