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

We previously reported that immunization with a synthetic peptide of human thyrotropin receptor (TSH-R) expanded humoral autoimmunity to TSH-R (Sugawa H, Ueda Y, Ueda M, Kosugi S, Ichiyama S, Mori T. Immunization with the 'immunogenic Peptide' of TSH receptor induces oligoclonal antibodies with various biological activities. Peptide 1998;19:1303-7.). In the present study, we examined this phenomenon at the T-cell level. Balb/c mice were immunized with a synthetic peptide corresponding to the C-terminal-specific insert of human TSH-R. Spleen cells were collected and subjected to antigen-specific ELISPOT assay. The number of interleukin 4-secreting cells specific to P354-367 increased within 3 weeks. Cells responding to the other peptides increased 7 weeks after immunization. This phenomenon was not observed in mice immunized with bovine serum albumin alone. During immunization, numbers of interferon-gamma-secreting lymphocytes were not changed significantly. These results indicated that immunization with C-terminal TSH-R-specific insert peptide causes fluctuation in the type 2 helper T-cell population but not type 1 Th cells against the TSH-R, and the recognition repertoire of type 2 helper T cell was expanded by the peptide.
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PMID:Expansion of helper T-cell recognition in mice immunized with a synthetic peptide corresponding to the C-terminal thyrotropin receptor-specific insert. 1049 26

In spite of the evidence that IL-10 has Th1-immunosuppressive and anti-inflammatory effects, it has been shown that IL-10 may reduce the tumorigenic capacity of certain tumor cell types. In order to characterize the responses elicited by IL-10, we explored the effect of transducing murine CT26 colon carcinoma cells with a recombinant retrovirus expressing mIL-10. IL-10 gene transfer of CT26 cells had no effect on tumor cell growth on plastic surface but inhibited the anchorage-independent growth capacity of tumor cells and their metastatic potential as assessed by their invasive and migration ability. Expression of IL-10 also elicited an antitumor immune response involving both CD4+ and CD8+ T cells. Assessment of the immune status of the animals demonstrated that mice injected with CT26-IL10 cells showed prevalence of a systemic and tumor-specific Th2 response. Spleen cells obtained from these mice showed an increased production of IL-4 and no changes in IFNgamma levels, characteristic of a Th2 response. These results demonstrate that IL-10 affects CT26 tumor cell growth by both inhibiting the malignant phenotype and by recruiting and activating a T cell-mediated antitumor response. This T cell response occurs in the context of a shift towards a Th2 response.
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PMID:IL-10 expression by CT26 colon carcinoma cells inhibits their malignant phenotype and induces a T cell-mediated tumor rejection in the context of a systemic Th2 response. 1051 19

The production and role of endogenous cytokines during the course of secondary Corynebacterium (C.) pseudotuberculosis infection were investigated in mice. When immunized mice were challenged on day 28 after primary infection, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were found to appear at 3 hr and to reach the maximum at 24 hr after challenge. Spleen cells of mice primarily infected from 2 to 8 weeks before produced a significant amount of TNF-alpha and IFN-gamma when stimulated with formalin-killed bacteria. However, they could not produce detectable amounts of IL-4. The administration of anti-TNF-alpha monoclonal antibody (MAb) and IFN-gamma MAb increased bacterial proliferation in the organs of immune mice and exacerbated the secondary infection. Injection of anti-CD4 MAb alone or anti-CD4 plus anti-CD8 MAbs resulted in significantly increased mortality and a marked suppression of bacterial elimination as well as cytokine production of secondarily infected mice, while the treatment with anti-CD8 MAb alone showed no effect on either the resistance or cytokine production of mice. These results suggest that CD4, probably Th1 T cells, play an important role for establishment of protective immunity against secondary C. pseudotuberculosis infection by secreting TNF-alpha and IFN-gamma.
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PMID:Tumor necrosis factor alpha and gamma interferon are required for the development of protective immunity to secondary Corynebacterium pseudotuberculosis infection in mice. 1059 77

Immune responses induced with helminth parasites have been extensively studied, but there is limited information on those to Fasciola hepatica, especially on the subtype of T cell induced with this parasite. We investigated the local and systemic T cell responses of different strains of mice following oral infection with doses of metacercariae from F. hepatica. Spleen cells from BALB/c and 129Sv/Ev mice given a low-dose (5 metacercariae) infection exhibited a Th2 response, producing high levels of the cytokines IL-4 and IL-5, and low levels of IFN-gamma and IL-2. In contrast, C57BL/6 mice showed a mixed Th1/Th2 response. A more marked polarization to a Th2 response was observed in BALB/c, 129Sv/Ev exposed to a high-dose (15 metacercariae) infection and the C57BL/6 mice also exhibited a clear Th2 response. IL-4 defective (IL-4-/-) C57BL/6 mice infected with 5 metacercariae produced less IFN-gamma and more IL-5 compared to their wild-type C57BL/6 counterparts, suggesting that IL-4 is important in establishing the Th2 type response in murine fasciolosis. However, the secretion of IFN-gamma and IL-2 was completely suppressed in the high-dose infection and this was also observed in IL-4-/- mice. Thus, liver flukes may secrete molecules that downregulate Th1 responses. T cell responses in the mesenteric (MLN) and hepatic lymph nodes (HLN) were also examined since newly excysted juveniles infect through the intestinal wall of their host before migrating to the hepatic tissue. Cells from both MLN and HLN secreted higher levels of IL-4 and IL-5 compared to spleen cells. We also observed a difference in cytokine profiles secreted by the MLN and HLN, which may reflect responses to antigens liberated by newly excysted juveniles and hepatic stage parasites, respectively.
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PMID:Fasciola hepatica infection downregulates Th1 responses in mice. 1067 96

Previous studies have described an oral influenza vaccine comprising whole irradiated virus and an erythrocyte complex (IV-EC), which gave broad-based protection against influenza virus challenge in mice. The present study examined the immune responses generated after live virus challenge of vaccinated mice, particularly to determine whether mice vaccinated with IV-EC had enhanced CTL activity to compensate for the previously reported diminution in lung IgA response. Oral vaccine groups examined were IV-EC, live virus alone (LV) or live virus-erythrocyte complex (LV-EC), compared with irradiated virus and erythrocyte alone controls. The antibody responses of IV-EC and LV-EC vaccinated mice showed significantly elevated lung and serum IgG2a levels post live virus challenge, with no comparable increases in IgG1 levels compared to controls. Spleen cells from IV-EC mice showed an enhanced post-challenge proliferative response to antigen compared with mice that had received live oral vaccines, indicating enhanced cellular activity post IV-EC immunization. However, CTL activity was not enhanced for IV-EC mice, and live virus-vaccinated mice had reduced CTL activity compared with controls, indicating that CTL were not important for post-vaccine protection. Cytokine analysis revealed a predominant IFN-gamma response in spleen cells from orally vaccinated mice, whereas IL-4 was not detected in any lung or spleen culture analysed. The results suggest, therefore, that protection from live influenza challenge after IV-EC or LV-EC vaccination was due to an IFN-mediated IgG2a response. Definitive confirmation of the role of these factors in post-vaccine protection can now be tested in IgG2a-depleted or IFN-gamma gene knockout mouse models.
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PMID:Studies on the IgA-independent immunological responses in mice to influenza virus challenge after oral vaccination with irradiated whole virus and an erythrocyte complex. 1076 15

To determine the importance of Th1 and Th2 cells in modulating granuloma formation, mRNA transcripts for Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-5) cytokines were assessed by the molecular technique of in situ hybridization in the liver granuloma. The molecular studies showed few number of cells expressing mRNA transcripts for INF-gamma whereas, considerable number of IL-2 cells were present in the liver granuloma at 6 weeks post-infection (p.i.). Complete disappearance of IFN-gamma expressing cells were found when the disease progressed to 13 weeks p.i. Conversely, very high number of cells expressing mRNA transcripts for IL-4 and fair number of IL-5 cells were present at 7 weeks p.i. with a peak level of IL-4 cells at 13 weeks p.i. These in situ molecular studies of the liver tissues, demonstrated that Th1 cells were present at the very early granuloma development. Moreover, Th2 cells were required for its full development. The main interesting finding was the number of cells expressing mRNA for IL-4, as they were very huge and it might exceed the total number of lymphocytes per se in the granuloma. Lymphocytes from experimentally infected mice-spleen cells were also cultured in vitro with S. mansoni soluble egg antigen (SEA) and the same cytokines of lymphocyte supernatant were measured by ELISA assay. The levels of IFN-gamma and IL-2 were high to 6 wk. p.i. with a slight decline of IFN-gamma, and increasing amount of IL-2 at 10-13 wk p.i. Spleen lymphocytes of fully formed granuloma secreted high levels of IL-4 and IL-5. The results suggest that the development of schistosome egg-induced liver granuloma is a complex process and both Th1 and Th2 cell subsets sharing with other inflammatory cells (non lymphocytes), may play an important role in regulating and modulating the immuno-pathology of granuloma formation and the subsequent hepatic fibrosis.
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PMID:Different cytokines profiles in spleen cells and liver granuloma of Schistosoma mansoni experimentally infected mice during disease development. 1078 35

Inbred mice of congenic strains that differ only in their H2 haplotype were used to examine the effects of MHC genes on production of cytokines. Spleen and lymph node cells were stimulated with mitogens in vitro, and cytokine protein was assessed by ELISA and/or bioassays. Cells from H2b mice synthesized less IL-3, IL-4, IL-5, TNF and IL-10 (less clearly) than the equivalent cells from H2k or H2d mice. Production of IL-6 by H2b spleen and lymph node cells was lower than that by cells from H2d mice. In addition, lower lymphoproliferative responses were observed in lymph node cultures from H2b mice. These effects were evident in congenic B10 and BALB strains. B10 H2b mice stimulated in vivo with anti-CD3 had lower levels of IFN-gamma and IL-5 protein in their serum compared with equivalent H2k and H2d mice. Because class I- or II-mediated antigen presentation was not required in our model, an immunoregulatory gene in the central MHC is implicated. Preliminary studies of MHC recombinant mice suggested that the gene or genes responsible lie telomeric of IEbeta. Evidence that the H2b haplotype carries an immunoregulatory allele with a small but consistent effect on cytokine production warrants further investigation.
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PMID:Lymphocytes from H2 mice produce lower levels of several cytokines than congenic H2 or H2 mice. 1084 12

In this study, we investigated the influence of different amounts of N-(palmitoyloxy) succinimide (PA-NHS): attachment of lipid tails to the protein and Quil A on the immunogenicity of the 38-kDa mycobacterial protein incorporated into immunostimulating complexes (ISCOMS; 38-kDa ISCOMS). The addition of higher amounts of Quil A during the ISCOMS preparation increased the amount of protein incorporated into ISCOMS, whereas the use of higher amounts of PA did not influence this parameter. Low antibody responses were observed after primary immunization with all 38-kDa ISCOMS preparations which, however, strongly increased after booster injections. IgG2a is the major subclass IgG induced by these ISCOMS preparations. There were only slight differences between the various ISCOMS formulations in their capacity to induce cytotoxic T-lymphocytes (CTLs). Spleen cells primed with ISCOMS prepared with the highest amount of Quil A produced high levels of IFN-gamma after stimulation with T helper cell type one (Th1) peptide of the 38-kDa protein (aa 70-84), 38-kDa protein or purified protein derivate (PPD). Spleen cells primed with ISCOMS prepared with the lowest amount of Quil A only substantial IFN-gamma levels were detected after stimulation with 38-kDa protein. IL-4 secretion was very low or not detectable with all ISCOM preparations. These results therefore demonstrated that all 38 kDa-ISCOMS preparations were: (1) immunogenic by inducing antibodies, Th1 and CTL responses; (2) that the way in which the ISCOMS were prepared, e.g. the amount of Quil A used, modulates the epitope specificity of the Th1 response.
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PMID:Induction of antibody and T-cell responses by immunization with ISCOMS containing the 38-kilodalton protein of Mycobacterium tuberculosis. 1092 94

A single large dose (15 kJ/m(2)) of UVB-irradiation induces systemic immunosuppression and tolerance. We previously reported that IL-12 promotes the accessory cell function of epidermal Langerhans cells. In this study we have examined whether IL-12-pretreated antigen-presenting cells (APC) could restore the diminished T-cell response in mice irradiated with a single large dose of UVB. Spleen cells from UVB-irradiated mice showed reduced IFN-gamma production in a hapten-specific response but the function of APC in non-exposed skin of UVB-irradiated mice was not impaired. The pretreatment of APC with IL-12 did not restore the impaired IFN-gamma production by T cells from UVB-irradiated mice. Neither IL-10 nor TGF-beta was found to be involved in the suppression. Instead, we observed that anti-CD3 mAb-induced IFN-gamma production by T cells from UVB-irradiated mice was not augmented in the presence of anti-CD28 mAb, whereas IL-4 production was enhanced by the addition of anti-CD28 mAb. Furthermore, the reduced IFN-gamma production by T cells from UVB-irradiated mice in response to antigen plus APC could be restored by adding IL-12 to the culture. Our results thus indicate that UVB-induced systemic immunosuppression involves impaired Th1-type responses of T lymphocytes through CD28 stimulation, and that IL-12 compensates for the impaired CD28 costimulatory signaling in T cells resulting in the restoration of Th1-type responses.
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PMID:Deficient Th1-type immune responses via impaired CD28 signaling in ultraviolet B-induced systemic immunosuppression and the restorative effect of IL-12. 1108 1

A study was conducted to evaluate the immunogenicity of the Brucella melitensis ribosome recycling factor (RRF)-homologous protein (CP24). The CP24 gene was cloned, expressed in Escherichia coli and purified. The resulting purified recombinant protein (rCP24) produced delayed-type hypersensitivity (DTH) reactions in B. melitensis-infected mice but not in naive controls. Thus, we decided to characterise the immune responses generated with DNA vaccination (pcDNACP24) or immunisation with the rCP24 in adjuvant. Animals injected with pcDNACP24 exhibited a dominance of IgG2a to IgG1 while mice injected with rCP24 developed a higher response of IgG1 than IgG2a. Both immunisation protocols were capable of eliciting CP24-specific gamma interferon (IFN-gamma) producing cells. Spleen cells from pcDNACP24-immunised mice did not produce interleukin (IL)-4, IL-10 or up-regulation of IL-2 mRNA. Cells from rCP24-immunised mice produced IL-10, up-regulated IL-2 mRNA but did not produce IL-4. Neither immunisation with purified CP24 nor injection of pcDNACP24 protected mice against challenge with live smooth B. melitensis. However, the potential of CP24 for a Brucella diagnostic test based on an in vitro antigen (Ag)-specific IFN-gamma production or DTH test would be worth testing.
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PMID:Immunogenicity of the Brucella melitensis recombinant ribosome recycling factor-homologous protein and its cDNA. 1185 76


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