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)

After peroral infection with cysts of Toxoplasma gondii, C57BL/6 mice died and A/J mice survived. To better understand the reasons for this difference in survival, host defenses during acute infection were studied: initial portal of entry of T. gondii contributed to susceptibility as more C57BL/6 mice survived after i.p. than peroral infection (p less than 0.001). Susceptible (C57BL/6) mice had more necrosis and inflammation in their brains, livers, and mesenteric lymph nodes than resistant (A/J) mice. Susceptible mice had less IgM antibody to T. gondii (p less than 0.0005) than resistant mice 7 days after infection, but amounts of IgG antibody to T. gondii were similar. Infection reduced percentages of spleen cells with the Lyt-2+ phenotype in susceptible (p less than 0.02) but not resistant mice; infection decreased percentages of spleen cells with the L3T4+ phenotype similarly in both strains of mice. Spleen cells from infected susceptible mice had greater depression in their blastogenic response to Con A (p less than 0.05) and produced significantly more IFN-gamma in culture with (p = 0.009) or without (p less than 0.05) Toxoplasma Ag than spleen cells from infected resistant mice. Infection increased serum levels of IFN-gamma substantially in susceptible but not resistant mice. Lymphocyte IL-2 production was similar in both groups of mice. Peritoneal macrophages from both strains of mice became activated to inhibit or kill T. gondii by 7 days after infection, but Kupffer cells became activated only in susceptible mice. These results indicate that increased resistance to peroral Toxoplasma infection is likely to be mediated by a number of immune responses acting together. They suggest that increased susceptibility may result from inadequately regulated inflammatory responses that increase tissue destruction.
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PMID:Immune responses associated with early survival after peroral infection with Toxoplasma gondii. 249 63

Lymphocytes of autoimmune mice have been reported to have defective IL-2 production and proliferation in response to the mitogen concanavalin A. We have examined transcription of lymphokine genes in Con A stimulated spleen cells from both autoimmune and normal mice and found that IL-2, IL-4 and gamma-interferon (IFN gamma) were induced in all mice tested. Spleen cells were taken from young (pre-disease) or old (clinically active) MRL/lpr (lpr) and male BXSB autoimmune mice and from their normal counterparts (MRL/n, BXSB females, BALB/c and DBA/2) and stimulated with Con A. Con A induced production of IL-2, IL-4 and IFN gamma message and protein, and kinetics of induction did not vary significantly among the strains. However, in old lpr mice, levels of IL-2 protein and mRNA were about 10-fold lower than in other strains; IL-4 protein and mRNA were decreased approximately three-fold; and IFN gamma mRNA was readily detected in unstimulated cells and low but detectable levels of protein were produced constitutively. In contrast, little or no defect in IL-2 or IL-4 transcription or secretion were seen in male BXSB mice and no constitutive IFN gamma transcription was seen in this strain. These data indicate that all three lymphokine genes are activated by Con A in autoimmune mice, even though Con A-induced proliferation is defective in these mice. Furthermore, autoimmune mouse strains vary in terms of lymphokine expression: male BXSB mice display a normal lymphokine profile, whereas lpr mice show a marked imbalance of lymphokines compared to normal controls.
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PMID:Expression of lymphokine genes in splenic lymphocytes of autoimmune mice. 250 45

Spleen cells from rats that have recovered from experimental autoimmune encephalomyelitis (EAE) suppress the production of IFN-gamma by effector T cells of EAE in an Ag-specific manner. These postrecovery suppressor cells also inhibit EAE in vivo. Fractionation of the postrecovery suppressor spleen cells on nylon wool and OX-8 coated plates yields a nylon wool-adherent CD4+ suppressor cell population that, when cocultured with effector T cells, suppresses IFN-gamma production by these effector cells. In contrast, the nylon wool-adherent, CD4+ postrecovery suppressor cell population fails to inhibit the production of IL-2 by the effector T cells. In further experiments, the effector T cell population was depleted of CD8+ cells and cocultured with the nylon wool-adherent, CD4+ postrecovery suppressor cells, and the supernatants were assayed for IFN-gamma and IL-2. IFN-gamma production was inhibited in these cultures but IL-2 production was not inhibited. Irradiated effector T cells were cocultured with CD4+ postrecovery suppressor cells, without myelin basic protein, in an effort to determine whether the mechanism of differential lymphokine suppression involved an anti-idiotypic response against effector T cells. No IL-2 was produced, indicating that there was no CD4+ suppressor cell mediated anti-idiotypic response against effector T cells. These studies suggest that the suppressor cell is a nylon wool adherent, CD4+ T cell that functions to down-regulate EAE effector T cells by differential inhibition of lymphokine production.
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PMID:CD4+ suppressor cells differentially affect the production of IFN-gamma by effector cells of experimental autoimmune encephalomyelitis. 257 35

Lymphoid cells from mice immunized i.v. or s.c. with Leishmania major antigens were analyzed for their capacity to produce lymphokines when stimulated with specific antigens in vitro. Spleen cells from BALB/c mice immunized by the s.c. route produced significantly higher levels of IL-3 and IL-3 mRNA than those from mice immunized by the i.v. route. The differential production of IL-3 was maintained at a wide range of antigen concentrations tested in vitro and for different culturing times. T cell enrichment procedures and treatment with CD4+ mAb in vitro confirmed the T cell nature of the IL-3 producer population. However, the IL-3 production in the two populations of spleen cells was equally high after Con A stimulation in vitro. The IL-2 production by the two populations of cells was also not significantly different after antigen or mitogen stimulation in vitro. To our knowledge, this is the first report of a differential synthesis of IL-3 mRNA and secretion of IL-3 induced by different routes of immunization followed by specific-antigen stimulation in vitro. These findings may also explain earlier observations that i.v. immunization with leishmanial antigen induces protection, whereas s.c. immunization leads to exacerbation of L. major infection, since IL-3 has been previously shown to promote leishmanial infection. The fact that the phenomenon also extends to other antigen systems suggests that this finding may have a broader implication in immune regulation and vaccine development.
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PMID:Distinct IL-3 activation profile induced by intravenous versus subcutaneous routes of immunization. 278 14

The effects of exogenously administered human recombinant IL-2 (hrIL-2) on resistance to Listeria monocytogenes infection were examined. Intravenous injection of hrIL-2 significantly enhanced antibacterial resistance in both BDF1 and C3H/HeJ mice. The beneficial effect of hrIL-2 was observed with as little as 0.6 micrograms per mouse, whereas optimum protection occurred at 6 micrograms per mouse, hrIL-2 was equally protective when administered concomitant with the listeriae or up to 24 h prior to infection; it had little effect if given after the bacterial challenge. Kinetic experiments indicated that both the peak bacterial burden and the time lag before L. monocytogenes began to be cleared from the spleen and liver were reduced in hrIL-2-treated mice as compared with control mice. Histopathological examination of spleens and livers confirmed that hrIL-2-treated Listeria-infected mice experienced considerably less damage to these organs than did control mice. Spleen cells from Listeria-infected mice exhibited depressed levels of mitogen-induced proliferation coincident with the peak bacterial burden in the spleen and liver and during the subsequent recovery from the infection. Administration of hrIL-2 to uninfected mice had no effect on spleen cell proliferation in response to mitogens in vitro, nor did hrIL-2 treatment restore normal levels of splenocyte proliferative responses to Listeria-infected mice. In addition, hrIL-2 treatment resulted in attenuated levels of serum colony-stimulating activity in infected mice as compared with control infected mice. Coadministration of both hrIL-2 and human recombinant interleukin-1 alpha at various dose and time combinations had no detectable additive or synergistic effect. Although these data do not suggest an obvious mechanism of action, they clearly demonstrate that hrIL-2 can augment host defense against the facultative intracellular pathogen L. monocytogenes.
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PMID:Treatment of mice with human recombinant interleukin-2 augments resistance to the facultative intracellular pathogen Listeria monocytogenes. 278 91

The pharmacokinetics and biodistribution of radioiodinated recombinant interleukin-2 (125I-IL-2) was studied after either intravenous (i.v.) or intraperitoneal (i.p.) injection into C57BL/6 mice. Beta-lactoglobulin radiolabeled with 131I served as a control protein. After i.v. injection, 125I-IL-2 preferentially accumulated in the liver and spleen. Liver accumulation was fast, peaking at 5 min, and was followed by rapid clearance. Spleen accumulation was slightly slower, peaking at 15 min. Blood values 1 min after i.v. injection were 22-34% of the injected doses (I.D.)/gram. These values declined quickly over the next hour. In contrast, after i.p. administration no organ showed specific uptake of 125I-IL-2. Blood values after i.p. injection were essentially constant over 3 h and were greater and more sustained than after i.v. administration. Kidney values for both 125I-IL-2 and 131I-beta-lactoglobulin, after either i.v. or i.p. injection, indicated that the major route of clearance for both compounds was rapid loss through the kidneys.
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PMID:Biodistribution and pharmacokinetics of recombinant, human 125I-interleukin-2 in mice. 278 99

Spleen cells from mice treated with LS2616 display a highly increased response to the polyclonal T cell lectin ConA. The total number of splenic T cells, and the relative ratios between L3T4+ and Lyt-2+ T cells were not altered by LS2616 treatment. By dissecting the overall ConA response it was found that the number of ConA-inducible, IL-2 reactive T cells was unaffected, while ConA-induced IL-2 production was enhanced after LS2616 treatment. Spleen cells from LS2616 treated mice, depleted of G10 adherent macrophages (M phi) and reconstituted with M phi from untreated mice displayed normal levels of ConA responses. M phi depleted spleen cells from untreated animals, cocultured with M phi enriched populations from LS2616 treated animals resulted in an increased ConA response. Furthermore, spleen cells from treated mice were found to be excellent stimulators for alloantigen-induced T cell responses; when used as responders in MLC, however, these cells were comparable to responders from non-treated animals. Taken together the results demonstrate that LS2616 exerts an immunostimulatory effect on M phi, which indirectly facilitates polyclonal and antigen-specific T cell responses. The possible implications of this observation on various immunoregulatory events are discussed.
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PMID:Mechanism of action of the new immunomodulator LS2616 on T cell responses. 295 30

Antigen-nonspecific suppressor T cells were identified in spleens of mice rendered unresponsive by sensitization of allogeneic antigen in combination with cyclosporine (CsA) treatment. Suppressor cells were obtained from C57BL/6 (B6, H-2b) mice treated with a single i.p. injection of 1 x 10(7) allogeneic P815 (H-2d) cells combined with a five-day course of CsA, a group that did not show any cytotoxic activity of spleen cells against P815 targets. These noncytolytic spleen cells displayed suppressor activity on the induction of cytotoxic T (Tc) cells of normal lymphocytes against not only P815 stimulator (80.9% suppression, P less than 0.01, responder:additional cell ratio = 2.5:1) but also third-party BW5147 (H-2k) stimulator (68.2% suppression, P less than 0.01). The unresponsive state appears to be due to suppressor T (Ts) cells that are nonadherent to plastic or nylon-wool, 1500 rads-sensitive, and Thy-1-positive. Capacities of spleen cells from CsA-P815-treated mice to release cytokines (interleukin 1 [IL-1]), interleukin 2 [IL-2], interleukin 3 [IL-3], and gamma-interferon [gamma-IFN]) were examined. Spleen cells from CsA-P815-treated B6 mice displayed 84.1%, 91.7% and 90.8% inhibition (0.35 +/- 0.07 U/ml, 1.4 +/- 0.29 U/ml, and 7.0 +/- 0.9 U/ml) of IL-1, IL-2, and gamma-IFN production compared with normal mice (2.2 +/- 0.54 U/ml, 16.9 +/- 2.1 U/ml, and 76.0 +/- 3.1 U/ml, P less than 0.01), respectively. However, IL-3 production was significantly less inhibition (46.1%, 2.35 +/- 1.0 U/ml in CsA-P815-treated mice and 4.36 +/- 1.7 U/ml in normal mice) compared with other cytokines (IL-1, IL-2, gamma-IFN). Two systems were employed to assess the immunosuppressive efficacy of antigen-nonspecific Ts cells in vivo. First, adoptive transfer (i.p.) of spleen cells harvested from CsA-P815-treated mice ten days after treatment on 3 consecutive days (days 0, 1, 2) at a 3 x 10(7) cell dose into virgin B6 mice that were immunized with P815 cells (1 x 10(7), day 0) completely inhibited the development of Tc cells against P815 targets (5% specific cytolysis, effector:target ratio [E:T] = 200). The suppressor effect was immunologically nonspecific; adoptive transfer of Ts cells from CsA-P815-treated mice also abrogated the development of Tc cells against third=party BW5147 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The in vivo immunosuppressive action of suppressor cells from alloantigen-cyclosporine-treated mice and the capacity of spleen cells to release interleukins and gamma-interferon. 296 48

It was the objective of these experiments to study the time-related changes in the responsiveness of the cellular elements of the immune system following contact with single non-H-2 or multiple H-2 histocompatibility antigens. The reactivity of spleen cells from mice that received injections of spleen cells bearing H-1c, H-3c, H-13a, or H-2b cell membrane alloantigens was characterized at intervals following antigen contact. Spleen cells taken from mice not receiving injections showed no in vitro proliferative or cytolytic responsiveness to cells bearing individual non-H-2 antigens; after in vivo antigen contact with single non-H-2 antigens there was an interval of specific cellular unresponsiveness followed by alternating periods of responsiveness and unresponsiveness. The duration of the unresponsiveness immediately following injection correlated with the strength of the injected antigen--specifically, the stronger the antigen, the shorter the period of unresponsiveness. The data indicate fluctuation in the level of helper T lymphocyte activity, as well as cytotoxic T lymphocyte activity. In contrast, in vitro responsiveness elicited by H-2b antigens with and without prior in vivo antigen contact was of a similar magnitude, and both persisted at a relatively constant level. Suppressor mechanisms were not studied. Of particular interest was the observation that in vivo contact with non-H-2 antigens resulted in suppression of spleen cell production of IL-2 in response to lectin stimulation and fluctuation in the magnitude of the primary response of cytotoxic T lymphocytes to H-2 antigens.
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PMID:Time-response studies of the cellular immune response to cell membrane antigens. 296 10

Spleen cells from B10.A mice transfused with B10.D2 blood suppress the immune responses of normal B10.A to B10.D2 in coculture as early as 2 days posttransfusion. In addition, the ability of B10.A mice to respond in cell-mediated lymphocytotoxicity (CML) is significantly impaired as early as 2 days after B10.D2 transfusion. Experiments were performed to characterize the cells mediating the suppressive effect and to determine whether the inability of transfused mice to generate a cytotoxic response is due to an inhibition of IL-2 production. To characterize the suppressor cells, spleen cells from B10.A mice were assayed 2 or 16 days after B10.D2 transfusion for the ability to suppress mixed lymphocyte culture (MLC) and CML responses of normal B10.A mice in coculture. The putative suppressor cells were either passed over a Sephadex G-10 or nylon wool column, treated with anti-Thy antibody or left untreated before addition to the coculture. Untreated cells from transfused mice suppressed the CML response of normal B10.A both 2 and 16 days posttransfusion, while the effect on the MLC response was inconsistent. Passage of the cells over Sephadex G-10 or nylon wool before assaying abrogated the suppressive effect, while treatment with anti-Thy antibody had no effect. These results suggest that the suppressor cells appearing shortly after blood transfusion have the characteristics of macrophages and not T lymphocytes. To determine the effect of transfusion on IL-2 production, cells from transfused mice were assayed for their ability to produce IL-1 and IL-2 and for the formation of IL-2 receptors. In addition, the effect of exogenous IL-1 and IL-2 on restoring the CML response of transfused mice to normal was assayed. The production of IL-1 by transfused mice was normal, while the production of IL-2 was significantly suppressed both 2 and 16 days posttransfusion. Activated cells from normal and transfused mice showed equal ability to absorb IL-2, indicating that IL-2 receptor formation is normal after transfusion. The addition of exogenous IL-2, but not IL-1, to CML cultures containing cells from transfused mice as responders restored the response to normal. These results indicate that the inability of transfused mice to respond in CML is due, at least in part, to an inability to produce IL-2. This could be mediated by prostaglandins released by activated macrophages.
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PMID:Effect of blood transfusion on IL-2 production. 296


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