Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Freshly isolated, mature dendritic cells (DC) from mouse lymphoid organs were analyzed by immunofluorescent labeling and flow cytometry to determine the number of discrete subpopulations and to assess possible lineage markers. The permanence of surface markers was then determined by overnight culture of the DC. Three DC subtypes were discerned, CD8alpha- DEC-205-, CD8alpha+ DEC-205+, and CD8alpha- DEC-205+, with different tissue distributions. The majority of DC expressed high levels of class II MHC, expressed CD11c, and expressed the costimulator molecules CD80, CD86, and CD40; CD80 and CD40 were further up-regulated on culture. DC also expressed low levels of L-selectin that were up-regulated on culture. Thymus contained predominantly CD8alpha+ DEC205+ CD11b- DC, resembling a major subpopulation of DC in other tissues but unique in expressing BP-1. Spleen contained predominantly two DC populations in equal proportions: one CD8alpha+ DEC-205+ CD11b- as in the thymus, and the other CD8alpha- DEC-205- CD11b+. Lymph nodes contained the same two DC populations as in spleen, but in addition a third population of CD8alpha- DEC-205+ CD11b- DC. The CD8alpha expression of splenic DC subpopulations did not change on culture. Although DEC-205 was up-regulated on culture so all DC became positive, the difference in the level between subpopulations was maintained. However, CD11b was up-regulated on culture, so all subpopulations became positive and finally expressed equivalent levels. Some aspects of this complex, but discrete, pattern of surface marker expression can be correlated with differences in lineage origin and functional activity of the DC.
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PMID:Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. 921 70

A long-term stroma-dependent culture system (LTC) has been developed which continuously produces hemopoietic cells providing an in vitro system for the study of cell differentiation. These nonadherent cell populations contain a large subpopulation of dendritic cells (DC). LTC producing DC were easily generated from spleen, but could also be established from bone marrow (BM) and lymph node with less success. It was difficult to establish DC-producing LTC from thymus. The properties of splenic and thymic stroma have been compared. Spleen stroma developed more complicated networks of fibroblasts, endothelial cells, macrophages, and DC. Thymic stromal monolayers were dominated by epithelial cells and fibroblasts, with a lower proportion of macrophages and endothelial cells. They had a relatively sparse structure of cell networks compared with spleen stroma. Cells with dendritiform morphology first appeared in cultures by 2-3 wk. The majority of cells produced were large cells which expressed DC-specific cell surface markers, major histocompatibility complex (MHC) Class II molecules, and the CD80/CD86(B7) costimulator. A high proportion of cells also expressed myeloid cell markers. No T or B lymphoid cells or granulocytes were present in the cultures. LTC continued to produce nonadherent cells resembling myeloid/DC for long periods, even after passage of stromal cells and stem cells at about 3-4 mo. after culture establishment. The LTC system offers potential to study the in vitro differentiation of myeloid/DC.
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PMID:Hemopoiesis in long-term stroma-dependent cultures from lymphoid tissue: production of cells with myeloid/dendritic characteristics. 959 May 3

The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 microg/ml haemocyanin and various concentrations of the agents. Low concentrations (<1.5 x 10(-4)M) of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 x 10(-4) M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 x 10(-4) M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 x 10(-4)M of the agents and the expression of molecules were examined by flow cytometer 24h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro.
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PMID:Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro. 1095 79

The influence of a macrolide antibiotic, roxithromycin (RXM), on co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with 8.0 micrograms of haemocyanin absorbed to 4.0 mg aluminum hydroxide were cultured in the presence of 100.0 micrograms/ml haemocyanin and various concentrations of RXM for 72 h. Low concentrations (1.0 and 2.5 micrograms/ml) of RXM did not influence cell activation induced by antigenic stimulation, whereas RXM showed a suppressive effect on blastic activity of the cells when the agent was added to the cultures at more than 5.0 micrograms/ml. RXM did not affect blastic activity of splenic T cells by anti-CD3 monoclonal antibody stimulation even when the cells were cultured in the presence of 10.0 micrograms/ml RXM. Addition of anti-CD80 and anti-CD86 monoclonal antibody to cell cultures caused significant suppression of cell activation by antigenic stimulation. We next examined the influence of RXM on co-stimulatory molecule expressions on splenic B cells in response to antigenic stimulation. Addition of RXM at a concentration of 5.0 micrograms/ml into cell cultures remarkably suppressed co-stimulatory molecule, CD40, CD80 and CD86, expressions, which enhanced by antigenic stimulation in vitro.
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PMID:Suppression of co-stimulatory molecule expressions on splenic B lymphocytes by a macrolide antibiotic, roxithromycin in vitro. 1146 Mar 18

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-based cancer cell vaccines have been shown to be potent inducers of antitumor immunity in several murine models, but the antitumor effects on established tumors have been minimal. Conversely, the major role of the heat shock protein gp96, localized in the endoplasmic reticulum (ER), is to act as a molecular chaperone to assist the folding of nascent polypeptide chains in the ER. gp96 derived from tumor cells elicits specific protective immunity against parental tumors, presumably through the transport of tumor-specific peptides to antigen-presenting cells and the maturation of dendritic cells (DCs). However, the therapeutic effects of tumor-derived gp96 on established tumors have not been promising. The present study analyzes the therapeutic effects of GM-CSF gene-transduced Lewis lung cancer (LLC/GM) cells combined with LLC-derived gp96 on established wild-type LLC tumors in immunocompetent C57BL/6 mice. Therapy with either irradiated LLC/GM cells or LLC-derived gp96 barely affected established LLC tumor growth. The antitumor effect was significantly enhanced when 1 microg of LLC-derived gp96 was administered together with 1 x 10(6) irradiated LLC/GM cells (p < 0.05). The antitumor effects of irradiated LLC/GM cells and LLC-derived gp96 required mainly CD8(+) T cells. Spleen cells obtained from mice vaccinated with irradiated LLC/GM cells and LLC-derived gp96 showed specific CD8 cytotoxic activities against LLC cells (specific lysis rate of approximately 28%). This antibody response was not associated with a synergic effect of the combination therapy. Moreover, draining lymph nodes from mice immunized with irradiated LLC/GM cells and LLC-derived gp96 contained more migrating mature CD11c(+) cells (higher levels of CD86 and major histocompatibility complex [MHC] class II molecules) compared with those from any other immunization protocols. These results suggest that the combination of irradiated LLC/GM cells and tumor-derived gp96 has potential as a new immunogene therapeutic strategy against lung cancer.
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PMID:Granulocyte-macrophage colony-stimulating factor gene-transduced tumor cells combined with tumor-derived gp96 inhibit tumor growth in mice. 1280 36

We have identified in the rat a new subset of MHC class II(+) CD4(+)CD3(-)CD11b(-) leukocytes that produce high amounts of type I IFN upon viral stimulation and that appeared homologous to plasmacytoid DC (pDC) previously described in humans and mice. These cells exhibited the following phenotype: CD5(+),CD90(+),CD45R(+),CD45RC(+),CD11c(-),CD161a(+),CD200(+),CD172a(+),CD32(+),CD86(+). Rat pDC did not express the DC-specific marker OX62 and were more abundant in the spleen than the classical CD4(+) and CD4(-) subsets of OX62(+)CD11b(+) DC we previously described that produced very little, if any, type I IFN. Spleen pDC exhibited an undifferentiated morphology and rapidly died in vitro, but showed extensive dendrite formation, survival, maturation, and moderate type I IFN production upon stimulation by oligonucleotides containing type B CpG motifs (CpG ODN). Type A CpG ODN and CD40 ligand induced pDC to produce large amounts of type I IFN, but did not promote maturation. CpG ODN and CD40 ligand, but not influenza virus, induced IL-12p40 and IL-6 secretion. Spleen pDC did not produce IL-12p70, TNF-alpha, IL-1beta, or IL-10 using these stimulation conditions. Correlating with their strong responsiveness to virus and CpG ODN, rat pDC specifically expressed Toll-like receptor 7 and 9 mRNA. Fresh spleen pDC were poor stimulators of allogenic CD4(+) and CD8(+) T cells, but became potent inducers of allogenic T cell proliferation as well as Th1 differentiation after stimulation by type B CpG. Therefore, rat pDC appear very similar to human pDC, indicating that the specific phenotype and functions of pDC have been highly conserved between species.
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PMID:Rat plasmacytoid dendritic cells are an abundant subset of MHC class II+ CD4+CD11b-OX62- and type I IFN-producing cells that exhibit selective expression of Toll-like receptors 7 and 9 and strong responsiveness to CpG. 1518 27

Dendritic cells (DC) are usually regarded as antigen-presenting cells (APC) involved in T cell activation, but DC also directly or indirectly affect B cell function, antibody synthesis and isotype switch. In this study, we explore potential of DC-based immunotherapy in ongoing experimental autoimmune myasthenia gravis (EAMG) in Lewis rats, which is mediated by anti-acetylcholine receptor (AChR) antibodies. Spleen DC were isolated from onset of Lewis rat EAMG on day 39 post immunization (p.i.), exposed in vitro to IL-10 and then injected intraperitoneally into ongoing EAMG Lewis rats at dose of 1 x 10(6) cells/rat on day 5 p.i. with AChR + complete Freund's adjuvant. IL-10-modified DC resulted in lower clinical scores, less body weight loss, lower numbers of anti-AChR IgG antibody-secreting cells and lower affinity of anti-AChR antibodies in rats receiving IL-10-modified DC, accompanied with lower expression of CD80 and CD86 and lower lymphocyte proliferation among lymph node mononuclear cells compared with control EAMG rats. Lower levels of IL-10 and IFN-gamma were also found in the supernatants of AChR-stimulated lymph node MNC culture in rats receiving IL-10-modified DC. These results demonstrate that IL-10-modified DC induced hypo-responsiveness by down-regulating co-stimulatory molecules, and reduced production of anti-AChR antibodies possibly by inhibiting IL-10 production. Importantly, this procedure that autologous DC from EAMG were adopted to treat ongoing EAMG is more close to clinical trial in human, encouraging future evaluation in human myasthenia gravis.
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PMID:Protective potential of experimental autoimmune myasthenia gravis in Lewis rats by IL-10-modified dendritic cells. 1519 2

Dendritic cell (DC)-based vaccine is a developing strategy to treat cancer including hepatoma. We evaluated the antitumor efficacy of vaccination with DCs pulsed with apoptotic cells, as compared to vaccination with DCs pulsed with cell lysates, in murine hepatoma models. Murine hepatoma cells, Hepa1-6, MH134 and BNL1ME.A.7R.1, and their syngeneic mice, C57BL/6, C3H/HeN and BALB/c, respectively, were used in the study. Protective and therapeutic antitumor effects of vaccination with bone marrow-derived DCs pulsed with irradiation or sulindac-induced apoptotic cells or cell lysates were analyzed. Immature DCs efficiently phagocytosed apoptotic cells and increased expression of CD86, a cell surface maturation marker. Vaccination with apoptotic cell-pulsed, but not cell lysate-pulsed, DCs promoted significant protective immunity against parental hepatoma in vivo. Spleen cells from mice vaccinated with apoptotic cell-pulsed DCs showed higher cytolytic activity and contained higher number of IFN-gamma producing cells against parental hepatoma cells than those from mice vaccinated with cell lysate-pulsed DCs in vitro. Polyriboinosinic polyribocytidylic acid [poly (I:C)], double strand RNA, further enhanced CD86 expression and the therapeutic efficacy of vaccination with DCs pulsed with apoptotic cells for pre-established hepatoma. These results suggest that vaccination with DCs pulsed with apoptotic cells and treated with poly (I:C) appears to be a promising approach as a new therapeutic means for hepatoma.
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PMID:Vaccination with dendritic cells pulsed with apoptotic cells elicits effective antitumor immunity in murine hepatoma models. 1580 23

Dendritic cells (DCs) play an essential role in the induction of immune responses to pathogen infections. Native DCs are difficult to obtain in large numbers and consequently the vast majority of DCs employed in all experiments are derived from bone marrow progenitors. In an attempt to solve this problem, we have established a novel CD8alpha(+) DC line (H-2(k)) from spleen, which we have named SRDC line, and which is easy to culture in vitro. These cells display similar morphology, phenotype and activity to CD4(-)CD8alpha(+)CD205(+)CD11b(-) DCs purified ex vivo. Toxoplasma gondii antigen was shown to be taken up by these cells and to increase class I and class II major histocompatibility complex (MHC), CD40, CD80 and CD86 surface expression. We report that vaccination with T. gondii antigen-pulsed SRDCs, which synthesize large amounts of interleukin-12, induced protective immune responses against this intracellular pathogen in syngeneic CBA/J mice. This protection was associated with strong cellular and humoral immune responses at systemic and intestinal levels. Spleen and mesenteric lymph node cell proliferations were correlated with a Th1/Th2-type response and a specific SRDC homing to spleen and intestine was observed. The SRDC or CD4(-)CD8alpha(+)CD205(+)CD11b(-) DC line can be expected to be a very useful tool for immunobiology studies of DC.
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PMID:A novel CD4-CD8alpha+CD205+CD11b- murine spleen dendritic cell line: establishment, characterization and functional analysis in a model of vaccination to toxoplasmosis. 1620 52

Royal jelly (RJ), especially its protein components, has been shown to possess immunomodulatory activity. However, almost nothing is known about the influence of RJ fatty acids on the immune system. In this work we studied the effect of 10-hydroxy-2-decanoic acid (10-HDA) and 3,10-dihydroxy-decanoic acid (3,10-DDA), isolated from RJ, on the immune response using a model of rat dendritic cell (DC)-T-cell cocultures. Both fatty acids, at higher concentrations, inhibited the proliferation of allogeneic T cells. The effect of 10-HDA was stronger and was followed by a decrease in interleukin-2 (IL-2) production and down-regulation of IL-2 receptor expression. Spleen DC, cultivated with 10 microg/ml of fatty acids down-regulated the expression of CD86 and the production of IL-12, but up-regulated the production of IL-10. In contrast, DC, pretreated with 100 microg/ml of 3,10-DDA, up-regulated the expression of CD86 and augmented the proliferation of allogeneic T cells. The highest dose (200 microg/ml) of both fatty acids which was non-apoptotic for both T cells and DC, down-regulated the expression of MHC class II and CD86, decreased the production of IL-12 and made these DC less allostimulatory. The immunosuppressive activity of 3,10-DDA was also confirmed in vivo, using a model of Keyhole lymphet hemocyanine immunization of rats. In conclusion, our results showed the immunomodulatory activity of RJ fatty acids and suggest that DC are a significant target of their action.
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PMID:Fatty acids isolated from royal jelly modulate dendritic cell-mediated immune response in vitro. 1763 Feb


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