UMLS:C0153470 - FACTA Search

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

Heat- or merthiolate-inactivated Trypanosoma equiperdum was administered to recipient mice that were subsequently challenged with viable inocula of the same stabilate. Only mice inoculated with merthiolate-killed parasites were completely protected from a challenge inoculum of 10(3) trypanosomes, an effect that was abolished by prior immunosuppression of mice. Immune sera from protected animals contained high levels of interferon (IFN)-gamma and specific IgG2a antibodies. Spleen cells from these mice produced high amounts of interleukin (IL)-2 and IFN-gamma in vitro in response to specific antigen or concanavalin A, whereas splenocytes from mice receiving heat-killed parasites produced high amounts of IL-6. In contrast, the production of tumor necrosis factor (TNF)-alpha and colony-stimulating activity (CSA) was not significantly different in mice receiving either killed parasite preparation. The protection in immunized mice was associated with the detection of strong delayed-type hypersensitivity (DTH) to T. equiperdum antigens, an effect that could be adoptively transferred onto naive recipients by specifically immune CD4+ lymphocytes. These results suggest that the development of protective immunity in mice to T. equiperdum by our immunization protocol may involve the activity of helper/DTH T cells, particularly those of the Th1 subset.
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PMID:Involvement of the Th1 subset of CD4+ T cells in acquired immunity to mouse infection with Trypanosoma equiperdum. 135 13

Granulomas around Schistosoma mansoni eggs are a principal cause of morbidity in mice infected with this helminth. In vivo treatment of infected mice with anti-IL-2 antibodies, with or without anti-IL-2 receptor antibodies, significantly diminished the size of circumoval granulomas in the liver and decreased hepatic fibrosis to half that in untreated mice. Antibody-treated animals also displayed a marked reduction in both peripheral blood and tissue eosinophilia while IgE levels were unchanged or increased. Spleen cell cytokine production in response to Ag or mitogen stimulation was selectively altered by in vivo anti-IL-2 administration. IL-5 responses were dramatically reduced, whereas IL-4, IL-2, and IFN-gamma responses were not consistently changed. These findings confirm previous observations, suggesting a role for IL-2 in egg-induced pathology but indicate that the primary function of this cytokine in schistosome-infected mice may be in the generation of Th2- rather than Th1-associated responses.
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PMID:Treatment with anti-IL-2 antibodies reduces hepatic pathology and eosinophilia in Schistosoma mansoni-infected mice while selectively inhibiting T cell IL-5 production. 153 55

Recent studies indicate that egg granuloma formation in murine Schistosoma mansoni infection is associated with Th2-mediated immune responses. The present study was designed to analyze dynamically the Th1 and Th2 responses in S. japonicum-infected animals and compare them with the results seen with S. mansoni. C3H mice were infected with 10 to 20 cercariae of S. japonicum and sacrificed 3 to 22 weeks later. Spleen cells were stimulated with parasite antigens (egg and adult worm) or the mitogen concanavalin A. Interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon (IFN-gamma) levels were measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA) or bioassays. Additionally, cytokine-producing cells were enumerated by ELISPOT. The results show that Th2 cytokine production, characterized by IL-4 and IL-5, represents the major response in the first month after egg laying begins, while the Th1 functions of IFN-gamma and IL-2 production are greatly depressed. However, by 22 weeks Th2 responses have diminished and IFN-gamma production in response to concanavalin A is apparent. IL-2 responses are minimal at all times. In vitro depletion of T-cell subsets indicates that CD4+ cells are the major subset responsible for production of IL-5 at 7 weeks of infection. These findings suggest that, as in the case of S. mansoni infection, S. japonicum-induced immunopathology is temporally associated with the host Th2 response, although other experiments indicate that IFN-gamma is also involved.
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PMID:Dynamic analysis of splenic Th1 and Th2 lymphocyte functions in mice infected with Schistosoma japonicum. 167 41

The role(s) of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-4 (IL-4) in establishment and maintenance of protective immunity to Francisella tularensis LVS in mice (C3H/HeN) was examined by selective removal of these cytokines in vivo with neutralizing antibodies. The 50% lethal dose (LD50) for mice infected intradermally with F. tularensis alone was 136,000 CFU; treatment of mice with anti-IFN-gamma or anti-TNF-alpha at the time of infection significantly reduced (P much less than 0.05) the LD50 to 2 and 5 CFU, respectively. Abrogation of protective immunity, however, was effective only when anti-IFN-gamma or anti-TNF-alpha was administered prior to day 3 postinfection. In contrast, the LD50 for mice treated with anti-IL-4 was repeatedly higher (555,000 CFU) than for controls; this difference, however, was not significant (P greater than 0.05). Thus, IL-4 may be detrimental, while IFN-gamma and TNF-alpha were clearly crucial to the establishment of protective immunity to F. tularensis during a primary infection. The importance of IFN-gamma and TNF-alpha during a secondary immune response to F. tularensis was also investigated. Spleen cells from immune mice passively transfer protective immunity to recipient mice in the absence of confounding antibody-mediated immunity. This passive transfer of immunity, however, was abrogated by treatment of recipient mice with anti-IFN-gamma or anti-TNF-alpha at the time of challenge infection. That anticytokines effectively abrogate protective immunity very early in the course of infection with F. tularensis suggests that T-cell-dependent activation of macrophages for microbicidal activity is unlikely. These T-cell-independent events early in the course of infection may suppress bacterial replication until a T-cell-dependent response ultimately clears the bacteria.
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PMID:In vivo modulation of the murine immune response to Francisella tularensis LVS by administration of anticytokine antibodies. 172 99

The adhesion receptors, LFA-1 and VLA-4, on lymphocytes mediate lymphocyte adherence to cytokine-activated endothelial cells (EC) in vitro. Based on our previous data, which suggested that the mAb TA-2 reacted with rat VLA-4, the effect of TA-2 on lymphocyte migration out of the blood was examined. Small peritoneal exudate lymphocytes (sPEL) preferentially migrate to cutaneous inflammatory reactions, whereas lymphocytes from peripheral lymph nodes (PLN) migrate poorly to inflammatory sites but home avidly to PLN. Treatment of sPEL with TA-2 inhibited sPEL migration to DTH, LPS, poly I:C, IFN-gamma, IFN-alpha/beta, and TNF-alpha by 35 to 65% and their accumulation in PLN by 50%. The homing of PLN lymphocytes to PLN was not inhibited by TA-2. Spleen T cell migration to cutaneous inflammatory sites was inhibited but homing to PLN was not affected. Systemic treatment with TA-2 inhibited sPEL migration to inflamed or cytokine-injected skin by up to 70%. Similarly, TA-2 strongly inhibited the migration of Ag-stimulated PLN lymphoblasts to skin and to PLN. The migration of lymphocytes from all sources, including the peritoneum, spleen, PLN, mesenteric nodes, and Peyer's patches, to mesenteric lymph nodes and Peyer's patches was inhibited by 80% and 95%, respectively. In conclusion, our results suggest that VLA-4 and possibly other alpha 4 integrins mediate the migration of the inflammation-seeking sPEL and Ag-activated lymphoblasts to cutaneous inflammatory sites and lymph nodes but do not affect the homing of PLN lymphocytes to PLN. These integrins also appear to be necessary for the migration of all types of lymphocytes to Peyer's patches and mesenteric lymph nodes.
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PMID:Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo. 175 94

Spleen cells of Mycobacterium lepraemurium-infected mice were cultured on petri dishes coated with mycobacterial antigens, and antigen-reactive cells were isolated. Upon incubation in mitogen- or antigen-free culture medium, these cells released mediators capable of depressing the in vitro proliferative response of normal splenocytes to specific antigen and to concanavalin A and lipopolysaccharide. One of these mediators was identified with gamma interferon (IFN-gamma), mainly on the basis that treatment of supernatants with monoclonal anti-IFN-gamma antibodies markedly reduced the suppressive activity contained therein. Detectable levels of tumor necrosis factor alpha (TNF-alpha) and TNF-beta were present in spleen cell culture supernatants of infected mice. Moreover, low doses of recombinant TNF-alpha and TNF-beta were found to potentiate the suppressive activity of exogenous IFN-gamma. Soluble T-cell receptors beta were also detected in the culture supernatants. The elimination of these molecules with monoclonal anti-T-cell receptor beta (F23.1) antibodies immobilized on a plastic surface partially reversed the depression of the response to mycobacterial antigen but did not affect the response to mitogens. These results revealed the complex nature of suppressor mediators that are produced by mycobacterial antigen-reactive cells and that regulate the in vitro proliferative response.
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PMID:A role for gamma interferon, tumor necrosis factors, and soluble T-cell receptors in the depressed blastogenic response of spleen cells of Mycobacterium lepraemurium-infected mice. 183 61

Macrophages are important regulatory cells that can both stimulate and down-regulate various immune functions. During syphilitic infection, these cells phagocytize, kill, and lyse Treponema pallidum. They also modulate early T cell activation by decreasing IL-2 production through secretion of PG. This report focuses on additional complexities of macrophage regulation. Non-adherent splenic cells were stimulated with Con A to induce IFN-gamma synthesis. High levels were detected in preparations from normal rabbits and much lower levels in preparations from infected rabbits. The organisms also readily stimulated IL-1 synthesis by adherent spleen preparations from normal but not from infected rabbits. When indomethacin was added to these latter preparations, this IL-1 defect was reversed, implicating PG in this down-regulation. Spleen cells were obtained from normal rabbits and from rabbits infected testicularly for 9 to 12 days. Infection elevated basal levels of class II Ia Ag on adherent cells. In addition, macrophage Ia expression was increased during 4 days of in vitro incubation with treponemes. Non-adherent spleen cells from infected animals inhibited two different macrophage functions. First, culture filtrates obtained after 48 h of incubation contained a soluble factor that subsequently decreased LPS-induced IL-1 synthesis. Second, when macrophages were co-incubated with non-adherent cells, treponemal stimulation of macrophage Ia expression was inhibited; this inhibition was reversed by indomethacin implicating prostaglandins in this down-regulation. In further experiments an exogenous source of IFN-gamma was incubated with adherent cells from infected rabbits. This stimulated macrophage function as shown by increased IL-1 synthesis and Ia expression and decreased PGE2 secretion. Results are discussed in terms of the complexities of immunoregulation by macrophages during syphilitic infection.
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PMID:Splenic macrophage function in early syphilitic infection is complex. Stimulation versus down-regulation. 190 94

The effects of transforming growth factor beta (TGF-beta) on interferon gamma-mediated killing of the intracellular protozoan parasite Trypanosoma cruzi and on the course of T. cruzi infection in mice were investigated. Spleen cells from mice with acute T. cruzi infections were found to produce elevated levels of biologically active TGF-beta in vitro, and the possibility that TGF-beta may mediate certain aspects of T. cruzi infection was then addressed. When mouse peritoneal macrophages were treated with TGF-beta in vitro, the ability of IFN-gamma to activate intracellular inhibition of the parasite was blocked. This occurred whether cells were treated with TGF-beta either before or after IFN-gamma treatment. TGF-beta treatment also blocked the T. cruzi-inhibiting effects of IGN-gamma on human macrophages. Additionally, treatment of human macrophages with TGF-beta alone led to increased parasite replication in these cells. The effects of TGF-beta on T. cruzi infection in vivo were then investigated. Susceptible C57BL/6 mice developed higher parasitemias and died earlier when treated with TGF-beta during the course of infection. Resistant C57BL/6 x DBA/2 F1 mice treated with TGF-beta also had increased parasitemias, and 50% mortality, compared with no mortality in infected, saline-treated controls. A single dose of TGF-beta, given at the time of infection, was sufficient to significantly decrease resistance to infection in F1 mice and to exacerbate infection in susceptible C57BL/6 mice. Furthermore, a single injection of TGF-beta was sufficient to counter the in vivo protective effects of IFN-gamma. We conclude that TGF-beta, produced during acute T. cruzi infection in mice, is a potent inhibitor of the effects of macrophage activating cytokines in vivo and in vitro and may play a role in regulating infection.
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PMID:Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factor beta (TGF-beta). 190 9

The production of gamma interferon (IFN-gamma) in response to infection and to a number of other agents was compared in Lpsn (C3H/HeN and C57BL/10ScSn) and Lpsd (C3H/HeJ and C57BL/10ScCr) mouse strains. Large differences in IFN-gamma production were observed between C57BL/10ScCr mice and the other mouse strains. With the exception of C57BL/10ScCr, all mouse strains, including C3H/HeJ, exhibited transient levels of IFN-gamma during infection with Salmonella typhimurium. Spleen cells of these mice, explanted on day 3 of infection, produced in vitro IFN-gamma spontaneously; this production was enhanced considerably by heat-killed S. typhimurium, heat-killed Propionibacterium acnes, concanavalin A (ConA), or lipopolysaccharide (LPS). These stimuli, except for LPS, also induced IFN-gamma production in cultures of normal spleen cells from noninfected animals. In contrast, C57BL/10ScCr mice produced no IFN-gamma following infection with S. typhimurium. Also, spleen cells of these mice, explanted on day 3 of infection, exhibited no spontaneous IFN-gamma production. A marginal response was obtained by additional stimulation of the cells with killed S. typhimurium, and a moderate response was obtained with ConA. Normal spleen cells from noninfected C57BL/10ScCr mice showed no IFN-gamma response to killed S. typhimurium, killed P. acnes, or LPS and only a low response to ConA. Impaired IFN-gamma production in C57BL/10ScCr mice was also evident during infection with Plasmodium chabaudi chabaudi, with which a low IFN-gamma response was seen only occasionally. Also, spleen cells from infected animals (days 2 to 8 after infection) exhibited only a very low level of IFN-gamma production in vitro; however, this production could be enhanced further by ConA. In comparison, C57BL/10ScSn mice infected with P. chabaudi chabaudi produced significant amounts of IFN-gamma. Spleen cells explanted from infected animals produced IFN-gamma spontaneously in vitro; this production was enhanced further by killed P. acnes and ConA. The results showed that in addition to the defect in LPS responsiveness, C57BL/10ScCr mice possess a defect in IFN-gamma production in response to different stimuli. During infection, IFN-gamma production and sensitization to LPS occurred in parallel. Infected Lpsn mice exhibited enhanced sensitivity and infected Lpsd C3H/HeJ mice exhibited reasonable sensitivity to the lethal effects of LPS. Lpsd C57BL/10ScCr mice remained resistant to LPS when infected with S. typhimurium and exhibited only marginal sensitivity when infected with P. chabaudi chabaudi.
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PMID:Gamma interferon production in endotoxin-responder and -nonresponder mice during infection. 191 3

In addition to previous evidence for the roles of T cell-dependent immunity and delayed-type hypersensitivity in acquired resistance to systemic candidosis in mice, in the present study we have investigated the relative contributions of L3T4+ and Lyt-2+ lymphocytes in the protective immunity induced by vaccination with low virulence Candida albicans cells. We have also addressed the issue of the mode of Candida Ag recognition by specific T cells leading to cytokine release. Spleen cells from immunized mice produced high levels of IFN-gamma in vitro in response to Candida Ag, and this activity was abolished only by the combined treatment of the responder population with anti-L3T4 and anti-Lyt-2.2 mAb plus C. Positively selected L3T4+ and Lyt-2+ cells also produced IFN-gamma in vitro, provided accessory cells (plastic-adherent and Thy-1- Ia- splenocytes, respectively) were added to the lymphocyte-yeast cell cocultures. The production of IFN-gamma by purified L3T4+ and Lyt-2+ cells was inhibited by addition of the respective anti-class II and anti-class I H-2 antibody to the cultures. In vivo, administration of anti-L3T4, anti-Lyt-2.2 mAb or a combination of both significantly impaired the resistance of immunized mice to challenge with virulent C. albicans, as manifested by increased recovery of the yeast from the mouse kidneys. A similar effect was observed upon neutralization of endogenous IFN-gamma by treatment with rat mAb. These results suggest that both L3T4+ and Lyt-2+ T cells play a role in acquired immunity to systemic C. albicans infection, and that their activity may involve IFN-gamma-mediated stimulation of candidacidal mechanisms.
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PMID:T cell subsets and IFN-gamma production in resistance to systemic candidosis in immunized mice. 197 Dec 96

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