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)

Our previous work has shown that cells of the immune system produce a growth hormone (GH) molecule similar to that secreted by the pituitary. In the present studies, we evaluated the possibility that normal spleen cells producing GH transferred to dwarf mice could stimulate their growth. The results showed that normal spleen cells alone or spleen cells treated with growth-hormone-releasing hormone (GHRH) did not appear to significantly stimulate the growth of dwarf mice. Spleen cells activated in vitro with concanavalin A or lipopolysaccharide and then transferred to dwarf mice, or thymus cells alone, were also without effect, whereas GH alone stimulated growth as expected. Serum levels of insulin-like growth factor-I (IGF-I) and IGF-I-liver RNA were undetectable in control dwarf mice and dwarf mice receiving spleen cells, whereas serum levels of IGF-I increased after treatment of dwarf mice with GH. The immune system of dwarf mice receiving spleen cells, however, was significantly altered. Spleen cells from dwarf animals showed enhanced immunoglobulin, interleukin (IL)-6, IL-2, and interferon-gamma production whereas no significant change was apparent in natural killer cell activity. Despite the absence of the pit-1 protein in dwarf mice, their spleen and thymus cells retained the ability to produce almost as much lymphocyte GH as normal. Overall, the findings support the idea that the pit-1 protein in lymphocytes of dwarf mice may not be obligatory for the expression of lymphocyte GH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the administration of growth-hormone-producing lymphocytes on weight gain and immune function in dwarf mice. 852 85

The development of infection seems to be influenced by the characteristics of antigen-presenting cells (APC) in the infection site. Thus, we compared the Semliki Forest virus (SFV)-antigen-presenting capacity of spleen cells, B-cell lymphomas, bone marrow-derived mast cells and nonparenchymal liver cells by measuring the production of lymphokines in SFV-specific T-cell hybridomas. Spleen cells were able to provide the signals needed to stimulate the production of IL-2, IL-4, IL-6 and IFN-gamma, while B lymphomas the signals leading to only IL-2 production. When bone marrow-derived mast cells were used as APC, SFV-specific T-cell hybridomas produced IL-2, IL-4 and IL-6 in the presence of soluble anti-CD3 antibody. However, no lymphokine production was detected when the SFV antigen was used instead of the antibody. Nonparenchymal liver cells containing liver endothelial cells and Kupffer cells have an APC function stimulating the production of IL-2 and IL-6. These findings confirmed that the T-cell hybridomas can be selectively stimulated by different APC to produce different lymphokines, and it would influence the development of the immune-mediated inflammatory response.
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PMID:Patterns of lymphokine production by Semliki Forest virus-specific T-cell hybridomas stimulated with different antigen-presenting cells. 853 9

The role of T helper 1 (Th1) and T helper 2 (Th2) responses in the murine acquired immunodeficiency syndrome (MAIDS) is unclear. It has been suggested that differential activation of T cell subsets, particularly a shift to Th2 cytokine production, may be associated with disease progression. To clarify the regulation of the cytokine network in the course of MAIDS, we examined the kinetics of cytokine production by isolated splenocytes. C57/BL6 mice were infected with the LP-BM5 mixture. The spleen cell proliferative response, together with IL-2, IFN-gamma, IL-10 and IL-4 production by unstimulated and ConA or anti-CD3 MoAb-stimulated spleen cells, were determined at various times after inoculation (weeks 1, 3, 6 and 9). Spleen cells isolated from murine leukemia virus complex (LP-BM5) infected mice spontaneously produced significant amounts of IL-2 and IFN-gamma one and three weeks post-infection, compared to uninfected controls. The capacity of isolated T cells to produce the Th1 cytokines IL-2 and IFN-gamma in response to stimulation with ConA and anti-CD3 MoAb decreased after 3 weeks of infection. The fall in IL-2 production ran parallel to the fall in the T cell proliferative response to ConA. IL-10 production in response to ConA and anti-CD3 MoAb increased after three weeks post-inoculation, and followed the reverse kinetic pattern to IFN-gamma and IL-2. In contrast, no significant spontaneous IL-4 production and no increase in IL-4 production in response to ConA or anti-CD3 MoAb occurred during the course of MAIDS, relative to uninfected controls. These results suggest that LP-BM5 infection leads to a fall in Th1 cytokine production rather than a clear switch to Th2 cytokine production.
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PMID:Kinetics of ex-vivo cytokine production by splenocytes during murine acquired immunodeficiency syndrome (MAIDS). 858 75

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

Cytokine profiles were determined following intranasal infection of C57BL/6J mice with murine gammaherpesvirus 68 (MHV-68). Spleen, mediastinal, and cervical lymph node cells from infected mice produced high levels of interleukin 6 (IL-6) and gamma interferon (IFN-gamma) and lower levels of IL-2 and IL-10 following in vitro restimulation. Little or no IL-4 or IL-5 was detected. Cytokine production was generally maximal at 10 days after infection, correlating with viral clearance from the lung, although significant levels were seen as early as 3 days after administration of the virus. In vitro infection of naive splenocytes induced B-cell- dependent secretion of IL-6 and IL-10, whereas IFN-gamma and IL-2 were produced only by cells that had been primed in vivo. Depletion of B lymphocytes from primed splenocyte populations did not, however, abrogate IL-6 and IL-10 production. Highly purified immune T cells made IL-6, IL-10. and IFN-gamma following in vitro restimulation with MHV-68. Thus, IL-6 and IL-10 are components of both the acquired and the innate host response. These cytokines have potential roles in the establishment and maintenance of persistent infection.
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PMID:Cytokine production in the immune response to murine gammaherpesvirus 68. 862 9

The aim of this work was to investigate the mechanism of spontaneous rat liver allograft tolerance. Liver allografts from a LEW donor into DA recipient (LEW-->DA) or of PVG-->DA were spontaneously tolerated (TOL) across a complete MHC mismatch. In contrast, DA-->LEW or PVG-->LEW liver allografts were rejected in 10 to 15 days (REJ). We examined whether donor cell migration to recipient lymphoid tissues might be associated with TOL. Many donor cells were observed in draining (celiac) lymph nodes (LN) and spleen, reaching a peak on day 1 and then decreasing rapidly thereafter. Irradiation of liver donors, which we have previously shown to delete tolerance, significantly reduced the number of donor leukocytes in recipient lymphoid tissues. While this suggested an association between donor cell migration and tolerance, the number, distribution, and type of donor cells in recipient lymphoid tissues of REJ was similar to those of TOL. Expression of cytokine mRNA in LN and spleen showed an early increase in the expression of IL-2 and IFN-gamma mRNA on day 1 and then a rapid decrease to constitutive levels. Spleen and LN levels of IL-6, IL-10, TNF-alpha, or TGF-beta mRNA showed much less up-regulation than IL-2 or IFN-gamma. Paradoxically, there was greater expression of IL-2 and IFN-gamma mRNA in TOL lymphoid tissues than in REJ, and this superinduction was partially prevented by donor irradiation. Superinduction of IL-2 and IFN-gamma was, therefore, more closely associated with TOL than was donor cell migration. This was confirmed by treatment of TOL recipients with a short course of methylprednisolone, which reduced survival of subsequent donor strain skin grafts. This finding has implications for treatment of human liver transplants and is evidence for a novel pathway of transplant tolerance.
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PMID:Tolerance to rat liver allografts. III. Donor cell migration and tolerance-associated cytokine production in peripheral lymphoid tissues. 864 43

Injection of goat anti-mouse IgD antibodies (GAM IgD) to mice has been shown to induce polyclonal IgG1 and IgE production by B cells and interleukin-4 (IL-4) production by goat Ig-specific T cells. Surface IgD cross-linking also activates B cells to function as antigen-presenting cells (APC). Although the GAM IgD treatment is a well-established system for analysis of B-cell dependent antigen presentation, the influence of GAM IgD treatment on the immune response to irrelevant antigens is not known. To address this issue, we analysed effects of GAM IgD treatment on (1) the mitogen response of freshly isolated T cells, and (2) the listerial antigen-specific response after immunization with viable Listeria monocytogenes, which induces CD4+ interferon-gamma (IFN-gamma) producing protective T cells in normal mice. Spleen CD4+ T cells from the GAM IgD-treated mice produced higher levels of IL-4 but lower levels of IFN-gamma and IL-2 than those from the control mice when they were stimulated with concanavalin A (Con A) in vitro. When spleen T cells were stimulated with listerial antigen 10 days after a low dose (1/20 LD50) of L. monocytogenes infection, CD4+ T cells from the GAM IgD-treated mice showed increased IL-4 production and decreased IFN-gamma and IL-2 production compared with those from the control L. monocytogenes-infected mice. Furthermore, the GAM IgD treatment resulted in a reduction of the survival rate after a high dose (1/2 LD50) of L. monocytogenes infection. These results suggest that treatment of mice with GAM IgD suppresses the T-helper type-1 (Th1)-type T-cell response and induces a Th2-type response against irrelevant antigens, even when they are injected after GAM IgD treatment.
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PMID:Suppression of T-helper type-1 immune response against Listeria monocytogenes by treatment of mice with goat antibodies to mouse IgD. 866 28

Cytokines and thymic hormones are thought to play critical roles in the regulation of T-lymphocyte development and function. In an effort to determine the effectiveness of such agents in an immunotherapeutic strategy, we employed aged mice in a hydrocortisone treatment model to generate an immunodeficient state and to study its reconstitution. Mice were given five daily injections of a natural cytokine mixture (NCM), recombinant interleukins (rIL-1, rIL-2) or their combination, thymosin alpha 1 or fraction 5 (T alpha 1, TF5), or the combinations of NCM plus T alpha 1 and of NCM plus TF5. Spleen and thymus weights were obtained and the cellular responses to stimulation in vitro with NCM, IL-1, IL-2 and mitogens (PHA and Con A) were assayed. Both NCM and T alpha 1 in vivo treatment augmented thymocyte and splenocyte in vitro responses to both interleukins and mitogens. Neither treatments with equivalent doses of rIL-1, rIL-2 nor their combination, nor TF5 achieved similar results. Of all the treatments, only NCM plus T alpha 1 augmented spleen weight; none augmented thymus weight. Surface marker analyses of T-lymphocytes and subsets indicate that treatment of mice with NCM plus T alpha 1 increased spleen T-cell numbers of both CD4 and CD8 positive cells significantly. These data indicate that NCM and T alpha 1 alone and in combination may be therapeutically useful to restore T-lymphocyte number or function in secondary immunodeficiency.
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PMID:Immunotherapy with natural interleukins and/or thymosin alpha 1 potently augments T-lymphocyte responses of hydrocortisone-treated aged mice. 870 47

Tolerance of MHC class II alloantigens can be achieved by intravenous injection of semiallogeneic hematopoietic cells into neonatal mice. Lymphoid cells of tolerant mice fail to proliferate or secrete interleukins IL-2 or IL-4 when stimulated in vitro with tolerogen. Since the lymphoid organs of B10.T(6R) tolerant mice contain normal levels of I-E reactive (V beta 11+) CD4+ T cells, deletion of alloreactive T cells does not appear to be the mechanism involved in the tolerance induction. To test whether T cells from tolerant animals can become activated under conditions that do not involve alloantigen stimulation, we stimulated these cells with immobilized anti-V beta 11 antibodies. Spleen cells from grafted tolerant and rejector mice proliferated in response to anti-V beta 11+ antibodies, suggesting they were not inert. We then tested whether V beta 11+ T cells from grafted mice can be induced to proliferate following stimulation with alloantigen in vivo. We adoptively transferred T cells from grafted tolerant and rejector mice into irradiated (B10.AQR x B10.T(6R))F1 mice and harvested the lymphoid organs after 65 h. Cells from both grafted tolerant and rejector mice underwent blast transformation, but only cells from rejector mice proliferated when exposed to immobilized anti-V beta 11 antibodies. The failure of V beta 11+ cells from tolerant mice to proliferate after in vivo stimulation may be because they are apoptotic. To test this hypothesis, spleen cells from naive or neonatally tolerized (with (B10.AQR x B10.T(6R))F1 cells) B10.T(6R) mice were adoptively transferred into irradiated (B10.AQR x B10.T(6R))F1 mice and bcl-2 expression was analysed in harvested V beta 11+ cells. Large cells recovered from recipients of naive 6R cells expressed bcl-2 mRNA. By contrast, large cells harvested from recipients of tolerized 6R cells did not express bcl-2 mRNA, suggesting bcl-2 mRNA expression was downregulated in these mice. Moreover, in another experiment, large V beta 11+ cells from grafted tolerant animals recovered after transfer into irradiated (B10.AQR x B10.T(6R))F1 mice did not express the bcl-2 protein as determined by flow cytometry, and contained fragmented DNA as assessed by the TUNEL method. Taken together, these data suggest that MHC class II tolerant T cells undergo apoptosis upon re-exposure to tolerogen in vivo.
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PMID:MHC class II tolerant T cells undergo apoptosis upon re-exposure to tolerogen in vivo. 876 18

Met-ase-1 is a 30 000 Mr serine protease (granzyme) that was first isolated in the cytolytic granules of rat CD3(-) large granular lymphocytes. We screened a mouse genomic library with rat Met-ase-1 cDNA, and obtained bacteriophage clones that contained the mouse Met-ase-1 gene. The mouse Met-ase-1 gene comprises five exons spanning approximately 5.2 kilobases (kb) and exhibits a similar structural organization to its rat homologue and a family of neutrophil elastase-like serine proteases. Mouse Met-ase-1 mRNA was only detected in total cellular and poly A mRNA of mouse CD3(-) GM1(+) large granular lymphocytes derived from splenocytes stimulated with IL-2 and the mouse NK1.1(+) cell line 4 - 16. Spleen T-cell populations generated by Concanavalin A stimulation and a number of mouse pre-NK and T cell lines did not express mouse Met-ase-1 mRNA. The 5' flanking region of the mouse Met-ase-1 gene also shares considerable regions of identity with the 5' flanking region of the rat Met-ase-1 gene. A 3.3 kb segment of 5' sequence flanking the mouse Met-ase-1 gene was inserted upstream of the chloramphenicol acetyltransferase reporter gene and this construct transiently transfected into a variety of mouse and rat large granular lymphocyte leukemia and T-cell lines. The transcriptional activity of the mouse Met-ase-1 5' flanking region was significant in the RNK-16 large granular lymphocyte leukemia, strongest in the 4 - 16 mouse NK1.1(+) cell line, and weak in several mouse pre-NK cell lines. Reverse transcriptase polymerase chain reaction of mouse large granular lymphocyte mRNA was used to derive the full-length coding sequence for mouse Met-ase-1. The predicted hexapropeptide of mouse Met-ase-1 (Asn-6 to Gln-1), was deleted by polymerase chain reaction mutagenesis to enable expression of active mouse Met-ase-1 in mammalian COS-7 cells. Northern blot analysis and protease assays of transfected COS cell lysates against a panel of thiobenzyl ester substrates formally demonstrated that the mouse Met-ase-1 gene encodes a serine proteinase that hydrolyzes substrates containing a long narrow hydrophobic amino acids like methionine, norleucine, and leucine in the P1.
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PMID:Cloning and expression of the recombinant mouse natural killer cell granzyme Met-ase-1. 878 Nov 19


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