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)

We have developed a murine model that facilitates the structural and functional analysis in vivo of dendritic cell (DC)-mediated phagocytosis of prostate epithelial cells. Recombinant human Flt3 ligand (rhFL) expands the number of dendritic cells in lymphoid and non-lymphoid tissues of mice. We show that rhFL also induced the ingress of dendritic cells into murine prostate, which involutes via epithelial apoptosis after surgical castration. Intact or castrated C57BL/6 and syngeneic transgenic adenocarcinoma of mouse prostate (TRAMP) mice were treated with rhFL or PBS control. Prostate and spleen were then studied by flow cytometry and immunohistochemistry. The number of prostatic CD11c+ and CD11b+ dendritic cells increased significantly in rhFL-treated mice compared with PBS-treated control mice and this effect was greatly augmented by castration of the mice. The immunophenotype of rhFL-mobilized prostatic cells was consistent with that of Langerhans cells (MHC class II+, CD11c+,CD11b+, DEC-205+, CD8 alpha-).MHC class II+ and CD11c+ dendritic cells that were present in the prostate glands of rhFL-treated and castrated C57BL/6 mice were intimately associated with TUNEL+ inclusions, which suggests that Langerhans-type dendritic cells in prostate participated in the clearance of apoptotic cells. Expression of MHC class II, CD54, CD80 and CD86 by prostatic dendritic cells was not up-regulated after castration and freshly isolated rhFL-induced prostate cells were unable to prime allogeneicT cells unless they were activated by culture either on plastic or with recombinant soluble CD40 ligand. Our data suggest that rhFL-mobilized prostatic dendritic cells resemble the functionally immature dendritic cells, which reside in peripheral tissues and contribute to the maintenance of peripheral tolerance.
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PMID:Flt3 ligand expands dendritic cell numbers in normal and malignant murine prostate. 1212 Dec 27

The failure of current BCG vaccine in controlling the global tuberculosis (TB) epidemic highlights an urgent need for improved TB vaccine formulations. In this study, we have investigated the effect of a novel adenoviral granulocyte macrophage-colony stimulating factor (GM-CSF) transgene-based adjuvant formulation (AdGM-CSF) on BCG vaccination in a mouse strain that is genetically weak responders to BCG vaccine. BALB/c mice were immunized subcutaneously (s.c.) with PBS, BCG, or BCG plus AdGM-CSF or control vector Addl70-3, the immunogenicity of BCG vaccine was evaluated by type 1 IFN-gamma production from lymphocytes of various lymphoid tissues upon mycobacterial antigen stimulation ex vivo. While mycobacterial antigen-specific IFN-gamma production was slightly enhanced by co-immunization BCG with Addl70-3 as compared to BCG immunization alone, a marked increase both in the magnitude and longevity of anti-mycobacterial type 1 immunity was observed in the local draining lymph nodes and spleens by immunization with AdGM-CSF-adjuvanted BCG. Furthermore, there was a significant increase in the number of mycobacterial antigen-specific IFN-gamma releasing CD4 T cells in mice immunized with AdGM-CSF-adjuvanted BCG vaccine. Consistent with these enhanced T-cell immunity and memory responses, AdGM-CSF-adjuvanted BCG vaccine significantly improved immune protection against secondary mycobacterial challenge. Our results suggest that GM-CSF transgene-based adjuvant formulation is an effective way to improve the immunogenicity of BCG vaccine.
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PMID:Enhanced immunogenicity of BCG vaccine by using a viral-based GM-CSF transgene adjuvant formulation. 1212 99

Peyer's patches (PP) represent a well-characterized inductive site in gut-associated lymphoid tissue that actively acquires antigens from the intestinal lumen. It was reported that organized PP are not required for antigen-specific IgA responses induced by oral immunization with soluble antigen mixed with the mucosal adjuvant, cholera toxin. However, the role of PP in the induction of mucosal and systemic immune responses remains to be clarified in the case of particulate antigen. Here, we created PP-null mice by treating them with monoclonal anti-IL-7 receptor alpha chain (IL-7 R alpha) antibody during gestation and then immunized with antigen-encapsulated poly-lactic acid (PLA) microspheres. Brisk OVA-specific antibody responses were noted in serum and fecal extracts of normal mice following direct intestinal immunization with OVA in PBS (OVA-PBS) as well as in PLA-microspheres (OVA-MS). Antibody production was similarly elevated in PP-null mice immunized with OVA-PBS via direct injection into the intestinal tract. In contrast, OVA-specific antibody responses were dramatically decreased in both serum and fecal extracts collected from PP-null mice immunized intestinally with OVA-MS. These results were further supported by the number of OVA-specific antibody-forming cells detected in the spleen and intestinal lamina propria. PP deficiency also resulted in the reduction in OVA-specific Th1/Th2 cell responses in the spleen and mesenteric lymph nodes of mice intestinally immunized with OVA-MS. These results suggested that organized PP do, in fact, play a crucial role in the induction of antigen-specific immune responses against ingested particulate antigen.
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PMID:Lack of antigen-specific immune responses in anti-IL-7 receptor alpha chain antibody-treated Peyer's patch-null mice following intestinal immunization with microencapsulated antigen. 1220 48

The use of receptor antagonists for chemokines is an alternative approach to blocking chemokine actions and has the potential to provide novel therapeutics. We determined the receptor antagonist properties of murine N-terminally truncated secondary lymphoid tissue chemokine (SLC)/6Ckine/CCR ligand 21 analogs and evaluated the preventive effects of SLC antagonists on chronic graft-vs-host disease (GVHD) in a murine model by blocking the homing of donor CCR7-expressing T cells into the recipient's lymphoid organs. SLC analogs truncated >4 aa residues from the N terminus showed a loss of chemotaxis and Ca2+ influx of CCR7-expressing cells and also inhibited SLC-stimulated chemotaxis and SLC-induced Ca2+ influx completely. To determine whether SLC antagonist inhibits the development of chronic GVHD, chronic GVHD was induced by injecting DBA/2 spleen cells into (C57BL/6 x DBA/2) F1 mice. Total numbers of spleen cells and host B cells, serum levels of IgE, and of total IgG and IgG1 of anti-DNA Abs in SLC antagonist-treated GVHD mice were significantly lower than those in control PBS-treated GVHD mice. This was due to a reduction in the levels of activated donor CD4+ T cells and a decrease in IL-4 production, resulting in a reduction in the numbers of activated host B cells. Therefore, our results suggest that SLC antagonist has beneficial effects for the prevention of chronic GVHD.
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PMID:Antagonist of secondary lymphoid-tissue chemokine (CCR ligand 21) prevents the development of chronic graft-versus-host disease in mice. 1249 47

In this study it was analysed whether intramuscular (IM) immunisation of piglets with F4 during the suckling period could protect against oral challenge with F4(+)-Escherichia coli and whether addition of 1alpha,25(OH)(2)D(3) or CpG-ODN could improve this protection.F4-seronegative F4-receptor positive pigs were divided into four groups of five pigs each. The pigs were intramuscularly injected with F4 fimbriae only or supplemented with 1alpha,25(OH)(2)D(3) (D(3)-group) or CpG-ODN (CpG-group). The control group received PBS in IFA. Seven days after the second immunisation, all pigs were intragastrically inoculated with 1 x 10(10) CFU of F4(+)-E. coli. All F4-injected groups, showed a reduced faecal excretion of F4(+)-E. coli. However, this reduction was only statistically significant in the D(3)-group 2 days post challenge. Pigs in the latter group showed a secondary antibody response upon challenge, indicating that F4-primed memory B-cells were present in the gut-associated lymphoid tissues at that moment.CpG-ODN, on the other hand, did not enhance the F4-specific antibody response. However, CpG-ODN significantly increased the F4-specific as well as mitogen-induced proliferation of peripheral blood monomorphonuclear cells indicating a direct or indirect overall effect on T-lymphocytes. In conclusion, supplementation with 1alpha,25(OH)(2)D(3) or CpG-ODN improved protection against an F4(+)-E. coli infection. This protection was most obvious for 1alpha,25(OH)(2)D(3) and indicates its potential use in veterinary vaccines against enteropathogens.
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PMID:Reduced faecal excretion of F4+-E coli by the intramuscular immunisation of suckling piglets by the addition of 1alpha,25-dihydroxyvitamin D3 or CpG-oligodeoxynucleotides. 1254 16

The hypothesis that prolactin (PRL) functions as an immunomodulator was based on studies showing lymphocyte PRL receptors, and its effects on growth, differentiation, and apoptosis in lymphoid cells. However, studies of PRL (PRL-/-) and PRL receptor knockout mice indicated that PRL was not required for immune system development or function under basal conditions. Because PRL maintains survival in glucocorticoid (GC)-treated Nb2-T lymphocytes in vitro, and PRL and GCs are elevated during stress, we investigated whether PRL protected T cells in vivo from GC-induced apoptosis. Adrenalectomized mice [PRL -/-, undetectable PRL; pituitary grafted PRL-/- (PRL-/-Graft), elevated PRL; and PRL+/-, normal PRL] were treated with dexamethasone (DEX) or PBS. Thymocytes and splenocytes were isolated and annexin V labeling of phosphatidylserine, DNA fragmentation, and caspase-3 activation were assessed as indices of apoptosis. Total thymocytes and CD4+ and CD8+ T cells obtained from DEX-treated PRL-/- mice exhibited significantly increased annexin V binding. In contrast, binding was not altered by DEX in PRL-/-Graft thymocytes. In addition, DEX induced classic DNA fragmentation in PRL-/- thymocytes. Elevated serum PRL reduced this effect. Thymocytes from DEX-treated PRL-/- mice exhibited increased caspase-3 activation, which was inhibited in cells from PRL-/-Graft mice. Finally, elevated expression of X-linked inhibitor of apoptosis, XIAP, was observed in thymi from DEX-treated PRL -/-Graft mice. This is the first demonstration that elevated PRL antagonizes apoptosis in thymocytes exposed to GCs in vivo. These observations suggest that, under conditions of increased GCs, such as during stress, elevated PRL functions physiologically to maintain survival and function of T-lymphocytes.
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PMID:Prolactin suppresses glucocorticoid-induced thymocyte apoptosis in vivo. 1269 19

Current evidence indicates an immunostimulating role for complex carbohydrates, i.e., polysaccharides, from several plant sources. In the present work, we determined the specific in vivo effects, with time of administration, of one such compound, a neutral arabinogalactan from larch not only on immune (lymphoid) cells, but also on natural killer (NK) lymphoid cells, as well as a variety of other hemopoietic cells in both the bone marrow and spleen of healthy, young adult mice. The latter were injected daily (i.p.) with arabinogalactan (500 microg in 0.1 ml pH 7.2 phosphate buffered saline-PBS) for 7 or 14 days. Additional, aged (1 1/2-2 yr) mice were similarly injected for 14 days only. Control mice were given the PBS vehicle in all cases, following the above injection regimen. Animals from all groups were sampled 24 h after the final injection and the immune and hemopoietic cell populations in the bone marow and spleen were assessed quantitatively. The results indicated that immediately following either 7 or 14 days of arabinogalactan administration to young, adult mice, lymphoid cells in the bone marrow were significantly decreased (p < 0.004; p < 0.001, respectively) relative to controls but remained unchanged at both time intervals in the spleen. NK cells, after 7 days of arabinogalactan exposure, were also decreased significantly in the bone marrow (p < 0.02), but unchanged in the spleen. After 14 days' exposure to the polysaccharide, NK cells in the bone marrow had returned to normal (control) levels, but were increased in the spleen (p < 0.004) to levels greater than 2-fold that of control. Among other hemopoietic cell lineages, none was influenced in the bone marrow or spleen by one-week administration of arabinogalactan; however, after two-week exposure, precursor myeloid cells and their mature (functional) progeny (granulocytes), were significantly reduced in the spleen (p < 0.043; p < 0.006, respectively), as were splenic monocytes (p < 0.001). These lineages in the bone marrow, however, remained steadfastly unaltered even after 14 days of continuous exposure to the agent. Of the vast cascade of cytokines induced in the presence of this polysaccharide, it appears that immunopoiesis- and hemopoiesis-inhibiting ones are most prevalent during at least the first two weeks of daily exposure.
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PMID:Effect over time of in-vivo administration of the polysaccharide arabinogalactan on immune and hemopoietic cell lineages in murine spleen and bone marrow. 1272 68

Altered IL-6 production regulation is associated with the pathogenesis of chronic inflammatory diseases, lymphoid malignancies, chronic infectious processes and certain types of autoimmune conditions. Here, we examine the effects of pollutants on IL-6 levels in mice serum and in culture supernatants of spleen cells. Mice were treated with vehicles (PBS or olive oil), benzo[alpha]pyrene (B[alpha]P, 100 mg/kg body weight), 2-bromopropane (2-BP, 3.5 g/kg), phenol (21.2 mg/kg), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 15 mg/kg). Serum IL-6 levels were significantly increased in the TCDD-treated group at 24 hours and 48 hours after a single exposure, whereas exposure to phenol, B[alpha]P or 2-BP did not cause a significant difference. IL-6 levels in culture supernatants of splenocytes were not affected at 24 hours and 48 hours after a single pollutant treatment. A repeated dose of TCDD (once/week for 4 weeks) resulted in a significant elevation of IL-6 levels in serum and its spontaneous production in culture supernatants of splenocytes. Repeatedly TCDD-treated mice contained more CD11b (Mac-1)-positive cells in the spleen and higher titers of tissue-specific autoantibodies than the vehicle-treated group. These results suggest that repeated exposure to TCDD might impair the regulation of immune response by deregulating the production of IL-6.
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PMID:Effects of benzo[alpha]pyrene, 2-bromopropane, phenol and 2,3,7,8-tetrachlorodibenzo-p-dioxin on IL-6 production in mice after single or repeated exposure. 1292 79

Plasmacytoid dendritic cells (DC) are known to produce large amounts of IFN-alpha when stimulated with virus in vivo and in vitro. Immunohistological staining of spleens from mice taken at different times after HSV infection revealed an early infiltration of plasmacytoid DC whereas both the myeloid DC and lymphoid-related DC had different kinetics. Upon rechallenge with virus in vitro, total splenic DCs from viral-infected mice were unable to produce IFN-alpha when compared with DC from mice that received an initial in vivo injection with PBS. Furthermore, DC from mice that were infected with increasing doses of HSV expressed high levels of accessory and activation molecules compared with control mice. However, when cultured in vitro together with allogeneic T cells, DC from mice that had been exposed to the highest viral titers in vivo induced the lowest levels of T cell proliferation. DC exposed to PBS in vivo promoted a Th1 response upon coculture with CD4(+) T cells whereas T cells cultured with DC exposed to increasing viral titers in vivo resulted in a gradually decreased Th1 response. The data suggest HSV induces DC maturation and at higher titers, exhaustion, diminishing T cell proliferation, and IFN-gamma secretion.
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PMID:Dendritic cells exposed to herpes simplex virus in vivo do not produce IFN-alpha after rechallenge with virus in vitro and exhibit decreased T cell alloreactivity. 1510 Feb 80

Pathogenic T cells in organ-specific autoimmune diseases use a limited number of TCR alpha- and beta-chains. In experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats by immunization with myelin basic protein, encephalitogenic T cells mainly use Vbeta8.2 TCR and clonal expansion of the Vbeta8.2 spectratype containing the EAE-specific complementarity-determining region 3 (CDR3) sequence, DSSYEQYFGPG, is found in the spinal cord throughout the course of clinical EAE. In the present study we performed temporal and spatial analyses of Vbeta8.2 spectratype expansion by CDR3 spectratyping and subsequent DNA hybridization with a probe specific for the encephalitogenic CDR3 sequence to elucidate the kinetics of encephalitogenic T cells during the induction phase after neuroantigen sensitization. It was demonstrated that Vbeta8.2 spectratype expansion and/or the positive signal in Southern blot were first detected in the regional lymph nodes as early as day 3 postimmunization and was disseminated over the lymphoid organs by day 6. Because perfusion of immunized rats with PBS erased the positive signals on day 3 postimmunization, the majority of Vbeta8.2-positive encephalitogenic T cells at the very early stage would reside within the lymphatic or blood vessels. Furthermore, removal of the draining lymph node 1, 3, and 6 days after immunization in the foot pad did not ameliorate clinical EAE. These findings strongly suggest that encephalitogenic T cells disseminate throughout the whole body very rapidly after sensitization. Analysis of pathogenic T cells at the clonal level provides useful information for designing effective immunotherapy.
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PMID:Tracking of V beta 8.2-positive encephalitogenic T cells by complementarity-determining region 3 spectratyping and subsequent Southern blot hybridization in Lewis rats after neuroantigen sensitization. 1538 83


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