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)

Lewis rats were rendered tolerant to ACI heart allografts using a regimen of posttransplant total lymphoid irradiation (TLI), rabbit antithymocyte or antilymphocyte globulin (RATG or RALG), and a single donor blood transfusion. All three treatment modalities were required to induce tolerance. The mechanism of the maintenance of tolerance was investigated by comparing the secretion of cytokines in the MLR, and the expression of cytokine mRNA in the allografts of tolerant and nontolerant Lewis rats. Although, the 3H-thymidine incorporation and secretion of IL-2 was frequently comparable in the MLR from tolerant and nontolerant rats, the secretion of IFN-gamma was markedly reduced in the tolerant rats. This was reflected in a markedly reduced frequency of cells expressing IFN-gamma mRNA in the allografts of tolerant as compared with nontolerant hosts. The frequency of cells expressing IL-2 and IL-10 mRNA was also reduced, but no significant difference was observed for cells with IL-4 mRNA. Spleen cells from nontolerant rats rapidly rejected ACI allografts in irradiated adoptive hosts, but spleen cells from tolerant rats did not. Evaluation of the cytokine mRNA expression at early and late time points in the allografts of adoptive hosts showed a pattern similar to that of the primary hosts. Thus, the tolerant state was associated with a maintenance or elevation of IL-4 expression and a marked reduction of IFN-gamma expression. Previous reports have shown that TLI alone induced this shift in the early recovery phase after irradiation.
 ...
PMID:Mechanisms of tolerance to rat heart allografts using posttransplant TLI. Changes in cytokine expression. 878 18

In BALB/c mice repeatedly infested with nymphal Ixodes ricinus ticks, lymphocytes from axillary and brachial lymph nodes which drain the tick attachment site produced significant levels of IL-2, TNF-alpha and GM-CSF when stimulated in vitro with Con A or anti-CD3 antibodies. Cytokine production by cells from lymph nodes of the opposite flank was equivalent to that of cells from uninfested mice. Nine days after the first infestation and IL-2, GM-CSF were produced primarily by the CD4+ T cells, while some other cell types contributed also to the TNF-alpha production. In mice repeatedly infested, a gradual increase of lymph node cell production of IL-2 was observed. The IL-2 levels regularly increased from the first to the third infestation compared to TNF-alpha levels which gradually decreased. The in vitro production of GM-CSF was not affected by successive infestations. Spleen lymphocytes from naive mice produced higher levels of IL-2 than lymphocytes from axillary and brachial lymph nodes. Both tick salivary gland extracts and D-mannose inhibited IL-2 production by these lymphocytes.
 ...
PMID:Cytokine production by lymph node cells from mice infested with Ixodes ricinus ticks and the effect of tick salivary gland extracts on IL-2 production. 884 33

Specific transplantation tolerance was induced in newborn mice by the intravenous injection of hematopoietic cells from semiallogeneic donors. Success of tolerance induction was tested by skin allografts. Spleen cells from mice bearing tolerated allografts for more than 60 days after transplantation spontaneously produced high levels of various cytokines. Production of both Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-10) cytokines, as well as of IL-3, was significantly increased in tolerant animals. The elevated production of Th1 cytokines was associated with the high secretory activity of CD4+ cells, while the production of Th2 cytokines was high in both CD4+ and CD8+ cell populations. The hyperproduction of cytokines was an intrinsic property of the T cells from tolerant animals and was not caused by a larger size of major T-cell subsets. The production of high levels of cytokines was a consequence of neonatal induction of tolerance and persisted for a long time after skin grafting of neonatally tolerized animals. These results show that neonatal induction of transplantation tolerance results in the production of enhanced levels of Th1 and Th2 cytokines which could be involved in the establishment and maintenance of immunological tolerance.
 ...
PMID:Production of high levels of Th1 and Th2 cytokines in mice with acquired transplantation tolerance. 892 48

Transfer factors (TF) are proteins that transfer the ability to express cell-mediated immunity from immune donors to non-immune recipients. The mechanisms of these effects have not been defined. The experiments described in this report were undertaken to test the hypothesis that a mechanism through which the beneficial effects of TF are expressed in clinical situation is through "education" of the immune system to produce certain cytokines in response to antigenic stimulation. BALB/c mice were sensitized to Herpes simplexvirus (HSV) either by sublethal systemic or cutaneous infections by administration of a HSV-specific TF. One week later their spleen cells were collected and single cell suspensions were stimulated in vitro with irradiated HSV or concanavalin. A Culture supernatants were collected and assayed for content of IL-2, IL-4, IL-10 and IFN-g. Spleen cells from infected mice responded to concanavalin A and to HSV by secreting large amounts of IL-2 and IFN-g, modest amounts of IL-10, and no IL-4. Transfer factor recipients produced similar cytokine profiles in response to concavalin A. These mice, however, responded to HSV by secreting IFN-g, but no IL-2. Thus, TF treatment selectively affects cytokine production in response to antigenic stimulation.
 ...
PMID:Profiles of cytokine production in recipients of transfer factors. 899 58

Our previous study demonstrated that Lewis (LEW) rat recipients engrafted with Brown-Norway (BN) rat liver displayed a long-term graft survival and that phenotypic and functional analyses of graft-infiltrating cells on day 6 postgrafting showed a lower proportion and activity of cytotoxic cells in long-term surviving hosts than LEW recipients engrafted with DA rat liver which showed acute rejection on day 9 postgrafting. In order to assess the immunological mechanisms of unresponsiveness, we analyzed the lymphocyte and serum from LEW recipients engrafted with BN liver. Spleen cells from tolerant LEW recipients on day 6 posttransplantation had no suppressor effect on the one-way mixed lymphocyte culture (MLC) reaction. On the other hand, when serum was added to MLC at a concentration of 6% of the total volume, it suppressed the mixed lymphocyte reaction (MLR) toward donor BN cells by 45.6%, but not toward third-party DA stimulator (-0.4%). Adoptive transfer of the serum from tolerant LEW hosts into the virgin secondary LEW hosts significantly prolonged the graft survival of BN kidneys from 7.8 +/- 0.2 to 14.7 +/- 1.6 days (p < 0.01), but not of third party DA kidney graft (mean survival time = 9.5 +/- 1.3 days). The in vitro study demonstrated that the suppressor factor in the serum inhibited the production of IL-2 as well as gamma-IFN in MLR. The suppressor factor was absorbed by LEW cells stimulated with BN cells in vitro, indicating that this factor was directed against recognition sites on responder T lymphocytes. These results showed that an antigen-specific tolerogenic factor which recognized the idiotype of the donor was released into the circulation through the process of BN liver grafting.
 ...
PMID:Immunological study of unresponsive state in rat hepatic transplant model. 2. Immunosuppressive factor in the serum from the tolerant hosts. 905 79

Staphylococcal enterotoxin B (SEB) is a bacterial enterotoxin able to simultaneously bind to class II molecules on APCs and to selected V beta regions (including V beta 8) of the TCR complex. Administration of SEB to adult BALB/c mice results in clonal activation of T cells bearing V beta 8 receptors, leading to an excessive release of proinflammatory cytokines. This initial immune response is followed by a long-lasting state of V beta 8-specific unresponsiveness, thought to benefit both the host (as it contributes to the down-regulation of the inflammatory response) and the bacterium (through ligand-specific T cell anergy). However, it is not clear how this type of restricted unresponsiveness can effectively impair the generation of an antibacterial response. To gain insight into the mechanism by which Gram-positive bacteria subvert the host immune response, we have investigated the immune competence of SEB-treated mice 48 h following SEB administration. We demonstrate in this report that in vivo, SEB induces a transient but profound state of unresponsiveness affecting both T and Ag-presenting cell functions. Although in vivo activation by SEB appears to be V beta-restricted under our experimental conditions, SEB-treated mice displayed an early (lasting 48 to 72 h postinjection) and V beta-unrestricted unresponsive state characterized by the inability to produce IL-2 in response to polyclonal TCR mitogens including third party bacterial superantigens (staphylococcal enterotoxin A and toxic shock syndrome toxin 1, SEA and TSST-1, respectively), Abs to non-SEB reactive V beta regions (V beta 6), anti-CD3 epsilon Abs, and a lectin (Con A). Spleen cell populations from SEB-treated mice also displayed defective APC functions, possibly related to a selective decrease in splenic dendritic cells numbers. Taken together, these observations indicate that SEB induces an early and transient state of immunodeficiency in vivo, representing a potential mechanism for escaping host immune surveillance.
 ...
PMID:Staphylococcal enterotoxin B induces an early and transient state of immunosuppression characterized by V beta-unrestricted T cell unresponsiveness and defective antigen-presenting cell functions. 905 96

In the present study an acidic polysaccharide ginsan, with a molecular weight of 150,000, devoid of lectin properties, was purified from Panax ginseng C.A. Meyer (Araliaceae). Ginsan induced the proliferation of T cells and B cells. Spleen cells became cytotoxic to a wide range of tumor cells without major histocompatibility complex-restriction after 4 or 5 days culture in vitro with ginsan. For the generation of these ginsan-activated killer (AK) cells adherent macrophages and CD4+ cells were needed as accessory cells. The generation of ginsan-AK cells was blocked in the presence of anti-IL-2, anti-IFN gamma, anti-IL-1 or anti-TNF alpha antibodies, showing the importance of these cytokines in the process. The surface phenotypes of the 4 day-cultured ginsan-AK cells was Thy1+, AsGM1+, CD8+, which is distinct from rIL-2 induced lymphokine activated killer (LAK) cells that were CD8. The ginsan also activated macrophages to produce reactive nitrogen intermediates and become tumoricidal. It also exhibited significant in vivo antitumor activity against B16 melanoma cells lines, and in the benzo(a)pyrene-induced autochthonous lung tumor model, at much lower doses than the maximum tolerate doses. Indeed, no mice died, which injected with ginsan at 1g/kg body weight intraperitoneally. In conclusion, 'ginsan' could potentially be an ideal nontoxic antineoplastic immunostimulator by activating multiple effector arms of the immune system.
 ...
PMID:Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng. 906 72

We investigated the production of IL-2 and IFN-gamma (Th1 type) and IL-4 (Th2 type) cytokines by mitogen-activated spleen cells from young, adult and old mice. Cytokine production was evaluated in culture supernatants by CTLL proliferation (IL-2), ELISA (IFN-gamma), CT4.S proliferation (IL-4) and in mRNA extracted from activated CD4+ cells by RT-PCR (IL-2, IFN-gamma and IL-4). Results show that the production of IL-2, as protein and mRNA, is profoundly depressed by aging, whereas that of IFN-gamma, as protein and mRNA, firstly declines and then increases with age. The production of IL-4, as protein, monotonically declines with aging whereas, as mRNA, firstly decreases and then increases above the level in young mice. Spleen cells in culture were also incubated with mitogens and with a recombinant cytokine (IL-1 beta, IL-2, IL-3, IL-4, IL-12 or IFN-gamma) at various concentrations. It was found that recombinant cytokines by and large enhance cytokine production when the level induced by mitogens only is low. This conclusion applies to IL-2 and IFN-gamma production as protein and mRNA. The addition of recombinant cytokines also increases the production of IL-4 at the protein level in spleen cells from old mice but, at the mRNA level, only in spleen cells from young mice. This finding suggests age-related changes in IL-4-specific mRNA transcription rate and post-transcriptional half-life as well as translation kinetics.
 ...
PMID:Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells. 908 80

Specific and non-specific parasite-induced changes in lymphocyte responses were analysed in C57/BL/6J mice after intrahepatic infection with Echinococcus multilocularis. Spleen cells harvested at selected times after infection were in vitro stimulated with mitogens or a crude soluble parasite extract (EmAg) at an optimized dose. Cell proliferative responses to Con-A were not modified by the infection over the first 22 weeks. In contrast, LPS-induced responses were decreased from the 13th week. A strong CD4+ proliferative T-cell response to the parasitic extract of infected mouse spleen cells was observed at the early stage of infection. This response then progressively decreased but remained significantly higher than that of control mice until the 19th week of infection. Cytokine production was investigated after in vitro EmAg stimulation of spleen cells. IFN-gamma, IL-2, IL-5 were produced within the first weeks after infection whereas the detection of IL-10 was slightly delayed. Thus, the promotion of the disease does not appear associated with the expansion of one rather than another T-cell subset in C57BL/6J mice. A general immunosuppression affecting both mitogenic and parasite-specific T-cell responses was observed at the end of the infection.
 ...
PMID:Characterization of T-cell immune responses of Echinococcus multilocularis-infected C57BL/6J mice. 922 82

Twenty weeks after moderate level infections with Schistosoma mansoni, approximately 20% of male CBA/J mice develop hypersplenomegaly syndrome (HSS) while the rest present with moderate splenomegaly syndrome (MSS). HSS and MSS mice differ pathophysiologically (degree of splenomegaly, anaemia, ascites, periportal fibrosis, portal hypertension) and immunologically with regard to antibodies (idiotypic expression, isotype levels) to schistosome soluble egg antigens (SEA), and spleen cell phenotypic profiles. This study compared in vitro proliferative responses and IL-2, IFN gamma, IL-4, and IL-10 production by spleen cells from uninfected mice and mice with acute (8 wk), MSS or HSS schistosomiasis mansoni, upon exposure to anti-CD3 epsilon or SEA, Spleen cells from uninfected mice produce Il-2 to anti-CD3 epsilon but exposure of cells from all three groups of infected mice to anti-CD3 epsilon or SEA led to only very low levels of supernatant IL-2. Anti-CD3 epsilon- or SEA-stimulated production of IFN gamma or Il-4, and anti-CD3 epsilon-stimulated production of IL-10, displayed similar patterns: highest cytokine production by cells from mice with acute infections and lower levels of production that did not differ between the two chronic groups. In contrast, while SEA-stimulated IL-10 production was again highest with cells from mice with acute infections, spleen cells from mice with MSS produced significantly more IL-10 than did those from mice with HSS. This association of low levels of antigen-induced IL-10 with severe pathology is consistent with the theory that IL-10 plays a role in the immunoregulation that occurs in chronic schistosomiasis.
 ...
PMID:IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni. 929 93


<< Previous 1 2 3 4 5 6 7 8 9 10