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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice infected with LP-BM5 murine leukemia viruses (MuLV) develop a syndrome with many features in common with AIDS including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. To evaluate cellular defects that may predispose infected mice to these sequelae, we studied the regulation of IFN gene expression. Spleen cells from mice infected with LP-BM5 MuLV expressed high levels of IFN-gamma mRNA by 1 wk post-inoculation and throughout the course of disease. By comparison, transcripts of IFN-alpha/beta genes were not detected in spleen cells at any time after infection. In uninfected mice, expression of IFN-alpha/beta genes is induced rapidly after infection with New-castle disease virus, but mice inoculated with LP-BM5 MuLV were unable to induce these genes by 4 wk after retroviral infection. Inhibition of IFN-alpha/beta induction due to LP-BM5 MuLV infection also occurred in nude mice, indicating this effect was not mediated by activated T cells. Furthermore, low levels of IFN-gamma transcripts were detected in spleens of nude infected mice, suggesting that cells other than T cells can express this gene. These results suggest that the normal contributions of IFN to control of microbial spread, immune surveillance, and lymphoid interactions are disrupted by infection with LP-BM5 MuLV.
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PMID:Abnormal regulation of IFN-alpha, -beta, and -gamma expression in MAIDS, a murine retrovirus-induced immunodeficiency syndrome. 284 90

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

We have presented 5 experimental observations which support a model for resistance to infection by the facultative intracellular bacterium, L. monocytogenes, in which the primary role for listeria-specific effector T cells is to cause recruitment of heightened numbers of macrophages and neutrophils which express potent anti-bacterial activity. These observations are: 1. Both macrophages and neutrophils, from mice and men, are bactericidal for listeria, salmonella, and E. coli. 2. When titrated, inflammatory macrophages and neutrophils have as much bactericidal activity as do immunologically-elicited macrophages and neutrophils. Thus "activated" macrophages are no better than inflammatory macrophages at killing bacteria. 3. Spleen T cells which transfer resistance to listeria also transfer, in a dose-dependent manner, the ability to accumulate enhanced numbers of neutrophils and macrophages following antigenic challenge. Phagocytes which accumulate following injection of immune vs. normal T cells kill bacteria equally well. 4. The major defect in mice which are genetically-susceptible to listeria is that they accumulate fewer macrophages and neutrophils in response to challenge with antigen or with an inflammatory agent than do mice which are genetically-resistant to listeria. 5. Macrophages induced to express bactericidal activity are not necessarily tumoricidal, and macrophages induced to express tumoricidal activity are not necessarily bactericidal. Thus bactericidal and tumoricidal properties of macrophages can be dissociated. Moreover, macrophages stimulated by recombinant IFN gamma to express tumoricidal activity do not express bactericidal activity.
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PMID:What T cells tell macrophages to do during resistance to listeriosis. 305 64

The mouse macrophage cell line J774 was easily infected by T. cruzi epimastigotes which were transformed to amastigotes that multiplied inside the cells. Spleen-T-cells from T. cruzi immune mice stimulated with Concanavalin A or T. cruzi, but not with unrelated antigens, released lymphokines into the supernatants that when added to J774 cells were unable to induce complete trypanocidal activity, although they were able to delay the rate of infection by protecting the cells from being infected. Addition of bacterial lipopolysaccharide (LPS), although inactive by itself, acted synergistically with the supernatants in inducing complete trypanocidal activity without affecting the susceptibility of J774 cells to infection. Gamma-interferon (gamma-IFN) activity was detected in the supernatants, however, but was not solely responsible for the trypanocidal inducing activities, since: there was no correlation between the levels of gamma-IFN and macrophage activation; gamma-IFN alone was less effective than the supernatants alone; and two active fractions of 100,000-150,000 mol. wt and 30,000 mol. wt were separated by gel filtration chromatography of the lymphokine preparations. The latter, which showed the characteristics of gamma-IFN with respect to size, pH 2 sensitivity and antiviral activity, had some trypanocidal activity alone. However, the 100,000-150,000 mol. wt fraction was active only in the presence of LPS. Finally, this trypanocidal inducing activity of the supernatants was not due to the induction of synthesis of gamma-IFN by the J774 cells.
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PMID:Activation by synergism between endotoxin and lymphokines of the mouse macrophage cell line J774 against infection by Trypanosoma cruzi. 310 22

The NK-1.1(-) mouse was constructed by weekly injections of monoclonal anti-NK-1.1 antibody from birth through adulthood. Spleen cells from these mice have decreased NK-1.1+ cells and null (Thy-1- and B220-) cells. Their splenic NK activity to YAC targets was low and was not enhanced by IFN-alpha or IFN-beta. Bone marrow (BM) of these NK-1.1(-) mice have normal precursors to NK cells: 1) NK activity could be generated from NK-1.1(-) BM cells cultured in rIL 2 for 5 to 6 days. These cultured BM cells expressed Qa-5, Thy-1, AsGm-1, and NK-1.1 antigens. The precursor cells of these BM cytotoxic cells are NK-1.1-; 2) transfer of BM cells from the NK-1.1(-) mice reconstituted the NK activity of irradiated, NK-depleted recipients. Lymphokine-activated killer cells could also be generated from spleens of these NK-1.1(-) mice. Therefore, the NK-1.1(-) mice were specifically depleted of mature cytotoxic NK cells, but not the NK-1.1- precursors of NK cells. This mouse model is valuable to study ontogeny and physiologic relevance of NK cells.
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PMID:The NK-1.1(-) mouse: a model to study differentiation of murine NK cells. 378 94

The requirement of CGF in the generation of cytotoxic cells against syngeneic tumor cells (T-9) and in the rejection of transplanted T-9 cells has been investigated. Spleen cells obtained from sensitized rats showed strong cytotoxicity against 51Cr-labeled T-9 cells upon incubation with CGF for 48 hr. Human recombinant IL 2 and rat IFN failed to generate cytotoxic cells from spleen cells of sensitized rats. CGF are produced by spleen cells upon inoculation of T-9 cells into sensitized rats as a host in vivo immune response. Production of CGF preceded the appearance of cytotoxic cells in regional lymph node and tumor tissues. In those rats, inoculated tumor cells were eventually rejected. In contrast, spleen cells failed to produce CGF upon inoculation of T-9 cells in unsensitized rats. Cytotoxic cells were not detected in unsensitized rats, and inoculated tumor grew in those rats. Thus, CGF is likely to be involved in the generation of cytotoxic cells and in the rejection of inoculated syngeneic tumor cells. A Mono Q anion-exchange column with an FPLC system allowed the chromatographic separation of CGF from IL 1, IL 2, IL 3, and CSF.
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PMID:Functional analysis of mononuclear cells infiltrating into tumors. II. Differential ability of mononuclear cells obtained from various tissues to produce helper factors that are involved in the generation of cytotoxic cells. 390 Feb 5

Spleen cell cultures derived from animals infected 6 d earlier with Listeria monocytogenes produced 10-20-fold more murine interferon gamma (MuIFN gamma) than spleen cells from nonimmune mice in response to stimulation with T cell mitogens. A striking temporal association was found between the enhanced synthesis of MuIFN gamma and the development of anti-Listeria immunity in that both the potential for increased MuIFN gamma production and the generation of Listeria-protective T cells developed and then decayed in unison. Treatment of spleen cells with monoclonal anti-Thy-1.2 plus complement virtually abolished the ability of cells from Listeria-immune mice to synthesize MuIFN gamma. The T cells producing MuIFN gamma were found to be more susceptible to complement-mediated lysis with monoclonal anti-Lyt-1.2 than with monoclonal anti-Lyt-2.2. The production of MuIFN gamma was not affected by treating spleen cells with anti-IgG antisera or with a monoclonal antibody directed against I-A specificities. MuIFN gamma was detected 4 h after the beginning of mitogenic stimulation of spleen cell cultures, and peak levels of MuIFN gamma were reached by 18 h. The IFN synthesized by mitogen-induced spleen cells derived from Listeria-immune mice were relatively labile at pH 2.0 and neutralized by a rabbit anti-MuIFN gamma serum but not by an antiserum having specificities for MuIFN alpha and MuIFN beta. The apparent molecular weight of the MuIFN gamma, as estimated by molecular sieving on a Bio-gel P-60 column, was estimated to be 38,000, and the isoelectric point as determined by chromatofocusing was extremely heterogeneous, ranging between pH 5.0 and pH 7.0.
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PMID:Enhanced production of murine interferon gamma by T cells generated in response to bacterial infection. 617 17

Spleen cells from BALB/c mice, immunized with SDS-acrylamide gel purified human fibroblast interferon (HuIFN-beta) were fused with mouse myeloma cells. Culture fluids from the resulting hybrid cells were screened for HuIFN-beta specificity by the following tests: a solid-phase RIA using partially purified HuIFN-beta, a protein-transfer RIA using electrophoretically resolved and immobilized HuIFN-beta, and a bioassay which tests residual HuIFN-beta activity in the supernatant following immunoprecipitation. Six HuIFN-beta-specific hybridomas were identified; two were capable of partially neutralizing HuIFN-beta activity. All six antibodies bind to the beta 1-IFN polypeptide synthesized in E. coli cells containing a cloned beta 1-IFN DNA sequence. All six monoclonal antibodies were found to be IgG3/kappa.
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PMID:Monoclonal antibodies directed against human fibroblast interferon: characterization and functional studies. 620 71

We have examined the relationship between the Con A-mediated induction of CTL effector function and immune IFN secretion in congenitally athymic nude mice. Spleen cells from young adult nude mice (2 mo of age) were found to require an exogenous source of IL 2 for the activation of a CTL effector response and for the release of immune IFN. However, the response of spleen cells from nude mice 9 mo of age differed from that of younger animals in that exogenous IL 2 was not required for the activation of CTL effector function and immune IFN secretion. Spleen cells from old nude mice were found to be capable of making IL 2 upon Con A stimulation similar to normal thymus-bearing animals. The data demonstrate that the maturation of IL 2-secreting cells can occur in athymic mice, that IL 2 is a requisite signal not only for the development of CTL effector function but also for the production of immune IFN, and that CTL effector function and immune IFN release are closely associated immunologic events.
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PMID:Secretion of immune interferon and generation of cytotoxic T cell activity in nude mice are dependent on interleukin 2: age-associated endogenous production of interleukin 2 in nude mice. 640 12

The effect of cyclosporin A (CsA) on the production of gamma interferon (IFN gamma) versus IFN alpha/beta was studied using mouse and human lymphocytes and fibroblasts. Spleen cells from C57Bl/6 mice produced low but significant levels (40-60 U/ml) of IFN gamma after 2 to 3 days of culture with irradiated DBA spleen cells. The addition of CsA at concentrations as low as 0.1 microgram/ml completely inhibited (less than 10 U/ml) IFN gamma production in these cultures. High levels of IFN gamma (170-1200 U/ml) were produced when either C57Bl/6 spleen cells or Ficoll-Hypaque-purified human peripheral blood lymphocytes (PBL) were cultured with the T-cell mitogen staphylococcal enterotoxin A (SEA). The addition of CsA (0.1 microgram/ml) to these cultures also completely inhibited (less than 10 U/ml) IFN gamma production. This inhibition was shown not to be due to a change in the kinetics of IFN gamma production or to a change in the amount of SEA required for stimulation. IFN gamma production in SEA-stimulated mouse spleen cells was inhibited at 3 days of culture even when CsA was added at 24 or 48 hr postculture initiation. Thus, CsA inhibits IFN gamma production even when early events associated with lymphocyte activation have been allowed to take place. In contrast to IFN gamma production, IFN alpha/beta production by Newcastle disease virus (NDV)-infected mouse and human lymphocytes or fibroblasts was not inhibited by the addition of CsA (1 microgram/ml). CsA also did not block the action of IFN gamma or IFN alpha/beta since addition of CsA (1 microgram/ml) to reference IFN standards had no effect on their antiviral activity. Thus, CsA inhibits the production of IFN gamma by T cells but appears to have no effect on the production of IFN alpha/beta by virus-infected cells or on the antiviral action of already produced IFN gamma and IFN alpha/beta.
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PMID:Cyclosporin A inhibits the production of gamma interferon (IFN gamma), but does not inhibit production of virus-induced IFN alpha/beta. 640 74


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