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)

In murine schistosomiasis, granulomas form around ova deposited in the liver and intestines of infected mice. The granulomas have eosinophils that produce vasoactive intestinal peptide (VIP) and T cells that display VIP receptors. IL-5 is a lymphokine important for the development and maturation of eosinophils. It seemed plausible that VIP, released from eosinophils, may interact with lymphocyte VIP receptors and modulate IL-5 production as part of a feedback regulatory circuit. Thus, we determined whether granuloma T cells make IL-5 and whether VIP modulates IL-5 production. Isolated granuloma cells enriched for T lymphocytes spontaneously released IL-5. Culture of these cells in the presence of VIP increased IL-5 secretion. Spleen cells were also studied. Spleen cells from infected mice did not spontaneously release IL-5 or express IL-5 mRNA and VIP did not stimulate these resting spleen cells to produce this IL. However, these cells did express IL-5 mRNA and secreted IL-5 in response to Con A or soluble egg Ag. VIP could not appreciably modulate IL-5 release when cells were cultured with VIP and the Ag or mitogen. Spleen cells washed free of Con A ceased IL-5 secretion within 24 h. These preactivated splenic T cells resumed vigorous IL-5 secretion in response to either Con A or VIP. Yet only Con A prominently induced IL-5 mRNA expression. VIP was an effective stimulus at concentrations equal to or above the kDa of the VIP receptor on both splenic and granuloma T cells (10(-8) M). It is concluded that, in murine schistosomiasis, VIP invokes IL-5 release from activated T cells that are not undergoing immediate TCR stimulation.
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PMID:Vasoactive intestinal peptide stimulates T lymphocytes to release IL-5 in murine schistosomiasis mansoni infection. 158 46

A recombinant strain of Listeria monocytogenes that stably and constitutively expresses Escherichia coli beta-galactosidase was used as a live vaccine vector. BALB/c mice were immunized orally or parenterally with the recombinant L. monocytogenes, and their cellular and humoral immune responses to beta-galactosidase were measured. Spleen cells taken 1 week after oral inoculation or 5 weeks after oral or parenteral inoculation (with a boost at 4 weeks) showed beta-galactosidase-specific CTL responses. The CTL line derived from mice immunized i.p. was also shown to be class I restricted and Thy-1.2+, CD8+, and TCR alpha beta+. All mice immunized with the recombinant L. monocytogenes had positive delayed-type hypersensitivity responses to heat-killed L. monocytogenes, but only 15% had a positive delayed-type hypersensitivity reaction to beta-galactosidase. Individual serum samples from mice immunized i.p. or i.v. were tested for antibody to beta-galactosidase. Approximately 11% had low positive titers for beta-galactosidase antibodies. These results demonstrate that both oral and parenteral immunization with recombinant L. monocytogenes results in a cellular immune response to the foreign protein, which is primarily a specific CD8+ CTL response.
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PMID:Induction of a cellular immune response to a foreign antigen by a recombinant Listeria monocytogenes vaccine. 160 62

There is now convincing evidence for the imposition of self tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we and other investigators have used transgenic technology to direct expression of a known "nonself" gene to a given extrathymic tissue. No lymphocytic infiltration was ever seen in transgene-expressing tissues, even if the mice were given normal syngeneic (nontransgenic) spleen cells intravenously or were stimulated with H-2Kb spleen cells. Infiltration did, however, occur in irradiated transgenic recipients of H-2Kb immune spleen cells. In MET-Kb mice, this infiltrate diminished with time, raising the possibility that peripheral tolerance may even have been induced in immune cells. H-2Kb-bearing skin was accepted in young RIP-Kb mice but rejected in older mice, which had lost more than 75% of their beta cells as a result of the overexpression of H-2Kb. This loss of tolerance thus occurred when the concentration of the tolerogen, H-2Kb, fell below some critical threshold. Following in vitro stimulation, spleen cells from young RIP-Kb mice could not kill H-2Kb-bearing targets, but could respond to third party targets. Thymus cells, on the other hand, could be stimulated to kill both targets, clearly indicating that tolerance was not imposed intrathymically. Spleen cells from older RIP-Kb mice (those that had lost most of their beta cells) killed both targets, which is in agreement with the in vivo data. Reactivity to H-2Kb was restored to young spleen cells by providing them with IL-2. Two hypotheses were proposed to account for the above findings: tolerance results either from the deletion or functional silencing of high-affinity effector cells or of regulatory, IL-2-producing helper T cells. As it is difficult to distinguish between these, we have produced a second series of transgenic mice (F3+) with rearranged TCR genes encoding an anti-H-2Kb TCR and derived "double-transgenic" (F3+RIP+) offspring by mating these mice with RIP-Kb mice. The transgenic TCR utilized the V beta 11 segment which can be detected by a monoclonal antibody. There were in the thymus very few CD4+ and very few CD4+8+ cells in both F3+ and F3+RIP+ mice and, in the double-transgenic mice, there was no evidence of deletion of CD8+V beta 11+ cells in the periphery although they showed tolerance to H-2Kb-bearing skin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A transgenic approach to the study of peripheral T-cell tolerance. 193 38

We prepared mAbs specific for the mouse Fas Ag (CD95) and used them to analyze the expression and apoptosis-inducing activity of the Fas Ag on murine immunocytes. Cytofluorometry of mouse bone marrow, thymus, and splenocytes using the mAbs indicated that cells of the T lineage, except for bone marrow cells, expressed Fas Ag on the surface. CD4-CD8- undifferentiated thymocytes expressed low levels of Fas Ag. Immature CD4+CD8+ thymocytes and mature CD4+CD8- and CD4-CD8+ thymocytes were highly positive for Fas Ag. CD4+CD8+ thymocytes were specifically sensitive to the apoptosis-inducing activity of anti-Fas, although CD4-CD8-, CD4+CD8-, and CD4-CD8+ thymocytes were resistant. Spleen T cells were resistant to anti-Fas, whereas they expressed Fas Ag. The superantigen, staphylococcal enterotoxin B (SEB) administered to BALB/c mice, induced clonal expansion and successive clonal deletion of spleen T cells bearing the V beta 8 TCR, which specifically reacts to SEB. Such clonal deletion of V beta 8 T cells was highly suppressed in lpr mice, which have defects in the Fas Ag gene. In SEB-administrated BALB/c mice, expression of Fas Ag was significantly enhanced on V beta 8, but not on V beta 6 T cells, which cannot react to SEB. Moreover, V beta 8 T cells in SEB-primed mice were sensitive to the cell-killing activity of anti-Fas, although V beta 6 T cells were resistant. These findings show that the expression level and apoptosis-inducing activity of Fas Ag on peripheral T cells are directly up-regulated by stimulation through the TCR in vivo.
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PMID:Expression and function of mouse Fas antigen on immature and mature T cells. 753 70

The present study was performed in order to define the responding populations and profiles of cytokine production in BCG-primed spleen cells restimulated in vitro with antigen. Spleen cells from DBA/2 mice, one of BCG-resistant strains (Bcgr), infected with Mycobacterium bovis BCG vigorously proliferated by restimulation with heat-killed BCG. This response peaked as early as on day 3 after BCG infection, and then decreased to the basal level by 3 weeks. Blocking of IL-2R alpha chain or IL-4 by each antibody partially inhibited it, but anti-IFN-gamma antibody did not, suggesting that both IL-2 and IL-4 were involved in the proliferation of primed spleen cells. CD4+ and gamma delta TCR-bearing T cell were responding populations to BCG, but CD8+ T cell was not, because depletion of CD4+ or gamma delta T cells by the treatment with each antibody and complement inhibited proliferation and IL-2/IL-4 production, but that of CD8+ T cells did not. Further study demonstrated that spleen cells from BCG-resistant DBA/2 mice produced more IL-2/IL-4 than those from BALB/c mice, one of BCG-susceptible strains (Bcgs), in response to BCG. These results suggest that both CD4+ and gamma delta TCR-bearing T cells play an important role in the host defense against M. bovis BCG infection, and that the magnitude of cytokine production is one of the critical factors to define the susceptibility of mice to this pathogen in the late phase of infection.
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PMID:[Analysis of antigen-specific proliferation and IL-2/IL-4 production of spleen cells from mice infected with Mycobacterium bovis BCG]. 776 May 38

C57BL/6 mice deprived or nondeprived of CD4+ and CD8+ T cells by mAbs were challenged with a rat T cell line, W7TM-1. Spleen cells obtained from CD4- and CD8-depleted animals rejecting W7TM-1 were examined by cytofluorometry, which demonstrated the presence of highly increased gamma delta type CD4-CD8- T cell population (30 to 50% of entire T cells). In vitro sensitization of these spleen cells with W7TM-1 generated a mixture of gamma delta and alpha beta type CD4-CD8- CTL for W7TM-1. Repeated stimulation of these cells with W7TM-1 resulted in a gamma delta-type T cell population with more than 95% purity by day 45. In contrast, alpha beta type CD8+ CTL for W7TM-1 were induced from mice nondeprived of CD4+ and CD8+ T cells. Both gamma delta-type CD4-CD8- CTL and alpha beta type CD8+ CTL were cytotoxic for rat cells in a species-specific manner. However, only reactivity of gamma delta type CD4-CD8- CTL, but not alpha beta type CTL, was inhibited by a mAb for TCR-gamma delta. The gamma delta type CD4-CD8- CTL clones were also prepared from spleen cells derived from CD4- and CD8-depleted mice. They were also reactive for xenogeneic cells in a species-specific manner. Spleen cells derived from CD4- and CD8-depleted mice rejecting the whole-layer rat skin grafts were in vitro sensitized with rat spleen cells, which also generated gamma delta type CD4-CD8- CTL specific for rat cells. V gamma 1 was detected as a major V gamma gene expressed in this gamma delta population by reverse transcriptase-PCR. Cytotoxicity for xenogeneic cells may represent one of major function of gamma delta T cells.
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PMID:Induction of murine gamma delta T cells cytotoxic for xenogeneic rat cells. 782 88

C57BL/6Kh mice were infected with a single i.p. injection of 1 x 10(5) FFU of LP-BM5 MuLV. The development and progress of the virus-induced lymphoproliferative disease was followed for 12 weeks after infection. As anticipated, progressive splenomegaly and lymphadenopathy, as well as almost total abrogation of immune responsiveness ensued. In contrast to previous reports, there was a dramatic increase in the frequency of CD4+ cells in spleens among which over 20% expressed V beta 5 TCR, as compared with fewer than 3% in spleens of normal mice. Spleen cells from infected mice retained their in vitro ability to proliferate upon stimulation with IL-2 and anti-CD3, but were unable to respond when stimulated with phorbol ester and either a low dose of IL-2 or calcium ionophore (ionomycin). A similar pattern of in vitro proliferative responses was obtained when normal spleen cells were treated with K252a compound, a known inhibitor of protein kinase C activity. Together with the observations that viral infection impaired down-regulation of the phorbol-induced kinase activity and that the kinase inhibitor only marginally enhanced suppression of virus-infected cells proliferation, this finding suggests that disturbances of protein kinase C activity may underly the pathological effects seen after viral infection. However, since no apparent quantitative and qualitative changes in protein kinase C itself and its translocation were observed, it is more likely that the virus may interfere with either the substrate or product of kinase activity.
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PMID:Acquired immunodeficiency in murine lymphoproliferative disease: considerations on pathogenesis. 808 52

In murine contact photosensitivity, a cutaneous delayed-type hypersensitivity reaction, preirradiation of the photosensitization site with UVB induced Ag-specific, afferent limb-acting, CD4+CD8- suppressor T cells (Ts). The present study examined usage of TCR V beta and production of immunosuppressive cytokines in Ts propagated in vitro. Spleen cells from UVB-preirradiated, 3,3',4',5- tetracholorosalicylanilide (TCSA)-photosensitized mice were stimulated with 3000-rad-irradiated lymph node cells (LNC) from TCSA/UVA-sensitized mice (LNCTCSA) in the presence of rIL-t. After several rounds of antigenic stimulation, a T cell line (B+TCL) consisted exclusively of CD3+CD4+CD8- V beta 7+ and V beta 13+ populations. Transfer to naive recipients of B+TCL treated with anti-V beta mAb plus complement revealed that the V beta 7+ cells suppressed both the in vivo and the in vitro aspects of contact photosensitivity to TCSA in an Ag-specific manner. The in vitro suppressive activity of B+TCL was neutralized by anti-IL-10 mAb, but not by anti-IL-4 mAb, indicating a crucial role of IL-10 in UBV-induced suppression. Upon stimulation with 3000-rad-irradiated-LNCTCSA, B+TCL released IL-4 and IL-10 but not IL-2, and V beta 7+ cells produced IL-10. The reverse transcriptase-PCR detected mRNA for IL-4 and IL-10 but not that for IL-2, IFN-gamma, or TGF-beta in B+TCL stimulated with or without concanavalin A. In accordance with the findings in B+TCL, spleen cells from UVB preirradiation plus TCSA/UVA mice contained V beta 7+ T cells that suppressed contact photosensitivity to TCSA and produced substantial amounts of IL-4 that provided a microenvironment for Th2 cell generation. We conclude that UVB preirradiation and photosensitization result in the generation of V beta 7+ Th2 cells that suppress contact photosensitivity by releasing IL-10. The dysfunction of effector Th1 cells underlying UVB suppression of delayed-type hypersensitivity seems to be due not only to altered APC function but also to counteraction of Th2 cells by Th1 cells.
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PMID:TCRV beta 7+ Th2 cells mediate UVB-induced suppression of murine contact photosensitivity by releasing IL-10. 859 33

To elucidate the funciton of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tl alpha 2-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tla2-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg. Tla2-3-1, Tg. Tla2-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg. Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tla2-3-1 and Tg.Tla2-3-2, respectively, expressed TCR gamma delta, whereas almost all those from C3H expressed TCR alpha beta. The MLC from Tg. Tla2-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg. Tla2-3-1 had little or none. The generation of gamma delta CTL recognizing TL in Tg. Tla2-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 gamma delta CTL clones were established from Tg. Tla2-3-2, whereas none were obtained from C3H. Of the 14 gamma delta CTL clones, 8 were CD8+ and 6 were CD4-CD8- double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCR gamma delta and CD3, and also by antibodies to CD 8 alpha and CD8 beta in CD8+ clones, showing that the activity was mediated by TCR gamma delta and coreceptors. The thymic origin of these gamma delta CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8 alpha beta heterodimers in CD8+ clones on their surfaces and by the usage of TCR V gamma 4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla2-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of gamma delta T cells.
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PMID:Positive selection of gamma delta CTL by TL antigen expressed in the thymus. 897 73

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.
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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


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