Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the modulatory role of IFN-gamma on the induction and maintenance of Th2 mucosal immunity in vivo, experiments were performed in mice lacking the IFN-gamma R. Aerosol OVA challenge of immunized wild-type mice resulted in an infiltration of eosinophils into the lung, associated with the ex vivo production of Th2 cytokines (IL-4 and IL-5) from purified lung Thy1.2+ cells stimulated via the CD3/TCR complex. However, while immunized IFN-gamma R-deficient mice exhibited elevated levels of IgE, IgG1, and reduced levels of IgG2a compared with wild-type mice, there was no difference in the recruitment of eosinophils into the lung or the production of IL-4 and IL-5 from lung T cells on day 3. In contrast, up to 2 mo after a single Ag challenge, eosinophils were still present in the lungs of IFN-gamma R-deficient, but not wild-type, mice. Likewise, lung-derived T cells from IFN-gamma R-deficient mice produced higher levels of IL-4 and IL-5, both at 1 and 2 mo after OVA challenge compared with T cells from wild-type mice. We conclude that endogenous IFN-gamma regulates the humoral isotype Ab pattern, but does not modulate the commitment of T cells to a Th2 phenotype in vivo or the acute infiltration of eosinophils to the lung. However, in the absence of IFN-gamma-mediated signaling, there is a transition from a spontaneously resolving to a persisting eosinophilic inflammation of the lungs, associated with a sustained capacity of lung T cells to secrete a Th2 cytokine profile.
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PMID:Mice lacking the IFN-gamma receptor have impaired ability to resolve a lung eosinophilic inflammatory response associated with a prolonged capacity of T cells to exhibit a Th2 cytokine profile. 860 83

Rat thymic dendritic cells (TDC) were isolated from thymic cell suspension by Nycodenz gradients of different densities and osmolarities. After cultivation of these cells for 3 days in the conditioned medium (TE-R 2.5 + HT supernatant) prepared by cocultivation of a medullary thymic epithelial cell line (TE-R 2.5) and hydrocortisone resistant thymocytes, the purity (75-85%) and survival of TDC significantly increased. The supernatant contained moderate activities of IL-1 and IL-6, low levels of TNF-alpha and IL-2 and factor(s) that strongly stimulated the proliferation of a mouse macrophage cell line RAW 264.7. TDC survival in culture was significantly increased by GM-CSF and decreased by IL-6 and IFN-gamma. The phenotype of TDC was studied by flow cytometry using a panel of monoclonal antibodies (mAb) to rat cell surface markers. It was found that almost all freshly isolated TDC expressed major histocompatibility complex (MHC) class I and class II molecules as well as CD45. Most TDC were LFA-1 (CD11a)+, CD18+, ICAM-1 (CD54)+ and CD53 (OX- 44)+, but only certain subsets expressed CD11b and thymocyte markers Thy1, CD2, CD4 and CD8. Upregulation in the expression of almost all the markers was observed after cultivation of TDC. In addition, cultivated, but not freshly isolated TDC expressed CD25 (IL-2R alpha) and CD45RC (OX-22) molecules. Cultivated TDC had strong accessory function in autologous thymocyte proliferation.
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PMID:Isolation, cultivation and phenotypic characterization of rat thymic dendritic cells. 862 79

Lethally irradiated Lewis (LEW) rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period, develop, upon withdrawal of CsA, a graft-versus-host-like disease, so-called CsA-induced autoimmunity (CsA-AI). This T cell-mediated autoimmune disease is thymus-dependent; it is generally held that this disease is a consequence of aberrant T cell recovery brought about by CsA. In this study we determined mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy1.1+, TCR alpha beta +) was observed as a consequence of CsA treatment, eventually resulting in decreased absolute peripheral T cell numbers. In these rats no altered CD4:CD8 T cell ratio was observed before onset of CsA-AI; CD4+ and CD8+ cells consisted predominantly of monocytes (CD4dim+, TCR alpha beta-) and natural killer cells (CD8+, TCR alpha beta-), respectively. LEW rats, x-irradiated, syngeneic bone marrow-reconstituted and treated with CsA, showed a marked and persistent, relative expansion of mature CD45RC+, RT6- Th cells. In contrast, Brown-Norway rats treated in a similar fashion, or LEW rats subjected to either CsA treatment or x-irradiation, did not show a comparable expansion of mature CD45RC+, RT6- Th cells, nor did these animals develop CsA-AI. The CD45RC+, RT6- Th cells produced IL-2, and moreover constituted the only Th subset producing IFN-gamma upon stimulation, and therefore were considered as Th1-like effector cells. These results are consistent with the view that a persistent preponderance of Th1 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.
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PMID:Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-gamma)-producing CD45RC+RT6- T helper cells. 880 39

The impact of social defeat on lymphocyte subpopulations and T helper subsets was investigated in Long Evans rats. CD4 T helper cell subsets with distinct functional properties and different cytokine profiles can be distinguished by using the mAbs OX-22 (anti-CD45RC) and OX-7 (anti-CD90, Thy1.1). Male intruders were exposed for 2, 6, or 48 h to aggressive resident pairs. All intruders were attacked upon introduction and were defeated as indicated by frequent display of full submissive postures. After 2 and 48 h of confrontation, drastic but differential effects on blood leukocyte numbers, CD4 and CD8a cells, and CD4 subsets were evident. However, after 6 h of confrontation most lymphocyte subset numbers corresponded to baseline levels. Focusing on CD4 subsets after 2 h of confrontation, we demonstrated that only the number of the CD45RC-CD90(-) subset declines, whereas neither the number of the CD45RC+CD90(-) subset nor the number of the CD45RC-CD90(+) subset (recent thymic emigrants) was influenced. Con A stimulation of sorted subsets identified the CD45RC-CD90(-) as a poor producer of IFN-gamma. The data clearly demonstrate that social factors might differentially influence not only T cell subsets but also T helper cell subsets with distinct cytokine profiles in a possibly time-dependent manner. Such a stress-induced shift toward a CD45RC+CD90(-)-dominated milieu may have important consequences in interpreting results obtained from mitogenic stimulation of blood lymphocytes and cytokine production profiles measured after such a stimulation. In addition, a shift toward a CD45RC+CD90(-) dominance may modify the type and magnitude of immune response, at least temporarily.
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PMID:Impact of social confrontation on rat CD4 T cells bearing different CD45R isoforms. 904 51

Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice make little IFN-gamma and show no Th1 polarization. This could signify that these granulomas have few cells capable of IFN-gamma synthesis or that such cells are under tight control. Granulomas can make IL-10 and TGF-beta, which can regulate IFN-gamma synthesis. Using FACS analysis and ELISA, we explored the origin and regulation of IFN-gamma in schistosome granulomas from both IL-4(-/-) and IL-4(+/+) mice. FACS analysis of intracytoplasmic IFN-gamma staining showed that some granuloma Thy1.2+ T cells (CD8+ and CD4+) express IFN-gamma. Granulomas had NK1.1+ cells, but they appeared to produce little or no IFN-gamma. Purified granuloma Thy1.2+ cells made IFN-gamma in vitro, whereas isolated NK1.1+ lymphocytes secreted little even with rIL-12 stimulation. Culture of granuloma cells with blocking anti-IL-10 or anti-TGF-beta mAb or with rIL-12 substantially increased T cell IFN-gamma synthesis, particularly in the IL-4(-/-) animals. Cultured granuloma cells depleted of Thy1.2+ lymphocytes by Ab and C released no IFN-gamma. It is concluded that granuloma IFN-gamma comes from T cells, not NK cells. Also, this T cell-derived IFN-gamma is subject to IL-10 and TGF-beta regulation, which is particularly evident in IL-4(-/-) mice. Thus, the Th2 granuloma of schistosomiasis has large numbers of activated Th1 or Th0 lymphocytes that are under tight restraint.
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PMID:Localization and regulation of IFN-gamma production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice. 959 Feb 48

Treatment with recombinant interleukin-3 (rIL-3) augmented IL-4 production of spleen cells in mice infected with Trichinella spiralis. In a previous report, we showed that treatment with rIL-3 accelerated IgE responsiveness in mice. We have examined IL-4 and interferon (IFN)-gamma production by spleen cells from both rIL-3-treated and untreated mice during the early stages of infection. The results indicated that IL-4 production was enhanced in rIL-3-treated mice compared to that in untreated mice. In contrast, there was no difference in IFN-gamma production between the two groups. Augmentation of IL-4 production was dependent on the dose of rIL-3 injected before infection. To examine if the treatment with rIL-3 affects T cell function, spleen cells from mice treated with various doses of rIL-3 were cultured under the stimulation with anti-CD3 (T cell receptor complex) mAb and then assessed for cytokine production. IL-4 production increased depending on the dose of rIL-3, while IFN-gamma production did not. Furthermore, spleen cells were separated by surface markers, Thy1.2, CD4 and CD8. Thy1. 2+ cell population responded significantly to produce IL-4 after anti-CD3 stimulation, when compared with IL-4 production of Thy1.2- cell population. A major producer of IL-4 in T cells was CD4+ cell population but not CD8+ cell population. IL-4 production was suppressed in rIL-3-treated mice injected with anti-CD4 mAb. These results suggest that IL-3 might play a role as Th2 amplifier in immune response to parasite infection.
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PMID:Exogenous interleukin-3 enhances IL-4 production by splenic CD4+ cells during the early stages of a Trichinella spiralis infection. 978 57

The most potent virulence factor of Pseudomonas aeruginosa, its exotoxin A (PEA), inhibits protein synthesis, especially in the liver, and is a weak T cell mitogen. This study was performed to correlate hepatotoxic and possible immunostimulatory features of PEA in vivo. Injection of PEA to mice caused hepatocyte apoptosis, an increase in plasma transaminase activities, and the release of TNF, IFN-gamma, IL-2, and IL-6 into the circulation. Most strikingly, liver damage depended on T cells. Athymic nude mice or mice depleted of T cells by anti-Thy1.2 mAb pretreatment failed to develop acute hepatic failure, and survival was significantly prolonged following T cell depletion. Neutralization of TNF or lack of TNF receptors prevented liver injury. In the liver, TNF was produced by Kupffer cells before hepatocellular death occurred. After T cell depletion, Kupffer cells failed to produce TNF. Transaminase release was significantly reduced in perforin knockout mice, and it was even elevated in lpr/lpr mice. These results demonstrate that PEA induces liver damage not only by protein synthesis inhibition but also by TNF- and perforin-dependent, Fas-independent, apoptotic signals.
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PMID:Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF. 982 May 56

Trypanosome-induced suppression of T and B cell responses to parasite-related and -unrelated Ags is considered a major mechanism of evasion of the host's immune defenses by the parasite. Reduced T and B cell responses have been attributed to suppressor T cells, suppressor macrophages, or both. We have previously shown that endogenously produced IL-10 and IFN-gamma mediate the suppression of T cell responses in Trypanosoma congolense-infected mice. Here, we show for the first time that splenic CD3+ Thy1.2+ alphabeta- gammadelta- CD4+ 8- and CD3+ Thy1.2+ alphabeta- gammadetla- CD4- 8- cells that copurify with plastic-, nylon wool-, or Sephadex G-10-adherent cell populations, in synergy with adherent Thy1.2- cells, are the major producers of IL-4, IL-10, and IFN-gamma in T. congolense-infected mice. We further demonstrate the involvement of these cells in the suppression of T cell proliferative responses to mitogen and in B cell responses to a parasite-unrelated Ag.
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PMID:Experimental murine Trypanosoma congolense infections. II. Role of splenic adherent CD3+Thy1.2+ TCR-alpha beta- gamma delta- CD4+8- and CD3+Thy1.2+ TCR-alpha beta- gamma delta- CD4-8- cells in the production of IL-4, IL-10, and IFN-gamma and in trypanosome-elicited immunosuppression. 983 5

The detection of T(H)1-type and T(H)2-type cells directly in situ would be of great value in the study of T(H) development and function in vivo. Transgenic mice expressing human Thy1 and mouse Thy1.1 under the control of the murine IFN-gamma and IL-4 promoters, respectively, have been generated. The hThy1(+) cells represent (with some temporal lag) most of the IFN-gamma-producing CD4(+) T-cells, while the mThy1.1(+) cells represent only a percentage of IL-4 secreting cells. This may be due to mono-allelic expression of the IFN-gamma and IL-4 genes. Since permeabilization is not required for the detection of the transgenic surface markers, these transgenic mice can facilitate the detection of T(H)1-type and T(H)2-type cells by flow cytometry with surface immunofluorescent staining. These surface markers should permit isolation of viable cells according to their T(H) type for adoptive transfer experiments, and may serve as a model system for tracing the development of T(H)1 and T(H)2-type cells in vivo.
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PMID:Transgenic mice expressing surface markers for IFN-gamma and IL-4 producing cells. 1100 Apr 2

Delayed lymphocyte infusions (DLIs) are used to treat relapse occurring post bone marrow transplantation (BMT) and to increase the donor chimerism in recipients receiving nonmyeloablative conditioning. As compared with donor lymphocytes given early post-BMT, DLIs are associated with a reduced risk of graft-vs-host disease (GVHD). The mechanism(s) responsible for such resistance have remained incompletely defined. We now have observed that host T cells present 3 wk after lethal total body irradiation, at the time of DLI, contribute to DLI-GVHD resistance. The infusion of donor splenocytes on day 0, a time when host bone marrow (BM)-derived T cells are absent, results in greater expansion than later post-BMT when host and donor BM-derived T cells coexist. Selective depletion of host T cells with anti-Thy1 allelic mAb increased the GVHD risk of DLI, indicating that a Thy1(+) host T cell regulated DLI-GVHD lethality. The conditions by which host T cells are required for optimal DLI resistance were determined. Recipients unable to express CD28 or 4-1BB were as susceptible to DLI-GVHD as anti-Thy1 allelic mAb-treated recipients, indicating that CD28 and 4-1BB are critical to DLI-GVHD resistance. Recipients deficient in both perforin and Fas ligand but not individually were highly susceptible to DLI-GVHD. Recipients that cannot produce IFN-gamma were more susceptible to DLI-GVHD, whereas those deficient in IL-12 or p55 TNFRI were not. Collectively, these data indicate that host T cells, which are capable of generating antidonor CTL effector cells, are responsible for the impaired ability of DLI to induce GVHD. These same mechanisms may limit the efficacy of DLI in cancer therapy under some conditions.
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PMID:Host T cells resist graft-versus-host disease mediated by donor leukocyte infusions. 1104 15


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