The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Warren Strober - One of the best experts on this subject based on the ideXlab platform.
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treatment of experimental trinitrobenzene sulfonic acid colitis by intranasal administration of transforming growth factor tgf β1 plasmid tgf β1 mediated suppression of t Helper Cell type 1 response occurs by interleukin il 10 induction and il 12 rec
Journal of Experimental Medicine, 2000Co-Authors: Atsushi Kitani, Ivan J Fuss, Kazuhiko Nakamura, Owen Schwartz, Takashi Usui, Warren StroberAbstract:In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor β1 (pCMV-TGF-β1) prevents the development of T Helper Cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-β1 protein does not have this effect. Intranasal pCMV-TGF-β1 administration leads to the expression of TGF-β1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-β1–producing T Cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These Cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-γ production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor β2 (IL-12Rβ2) chain expression. Coadministration of anti–IL-10 at the time of pCMV-TGF-β1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-γ secretion. However, anti–IL-10 leads to increased tumor necrosis factor α production, especially in established colitis. Taken together, these studies show that TGF-β1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rβ2 chain expression. In addition, TGF-β1 may also have an inhibitory effect on IFN-γ transcription.
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oxazolone colitis a murine model of t Helper Cell type 2 colitis treatable with antibodies to interleukin 4
Journal of Experimental Medicine, 1998Co-Authors: Monica Boirivant, Ivan J Fuss, Warren StroberAbstract:In this study we describe oxazolone colitis, a new form of experimental colitis. This model is induced in SJL/J mice by the rectal instillation of the haptenating agent, oxazolone, and is characterized by a rapidly developing colitis confined to the distal half of the colon; it consists of a mixed neutrophil/lymphocyte infiltration limited to the superficial layer of the mucosa which is associated with ulceration. Oxazolone colitis is a T Helper Cell type 2 (Th2)-mediated process since stimulated T Cells from lesional tissue produce markedly increased amounts of interleukin (IL)-4 and IL-5; in addition, anti–IL-4 administration leads to a striking amelioration of disease, whereas anti–IL-12 administration either has no effect or exacerbates disease. Finally, this proinflammatory Th2 cytokine response is counterbalanced by a massive transforming growth factor-β (TGF-β) response which limits both the extent and duration of disease: lesional (distal) T Cells manifest a 20–30-fold increase in TGF-β production, whereas nonlesional (proximal) T Cells manifest an even greater 40–50-fold increase. In addition, anti–TGF-β administration leads to more severe inflammation which now involves the entire colon. The histologic features and distribution of oxazolone colitis have characteristics that resemble ulcerative colitis (UC) and thus sharply distinguish this model from most other models, which usually resemble Crohn's disease. This feature of oxazolone colitis as well as its cytokine profile have important implications to the pathogenesis and treatment of UC.
Andrew N J Mckenzie - One of the best experts on this subject based on the ideXlab platform.
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t1 st2 deficient mice demonstrate the importance of t1 st2 in developing primary t Helper Cell type 2 responses
Journal of Experimental Medicine, 2000Co-Authors: Michael J Townsend, Padraic G Fallon, David John Matthews, Helen E Jolin, Andrew N J MckenzieAbstract:We have generated mice with a deficiency in T1/ST2 expression to clarify the roles of T1/ST2 in T Helper Cell type 2 (Th2) responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of T1/ST2-deficient mice with those generated by wild-type mice. Using a primary pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that granuloma formation, characterized by eosinophil infiltration, is abrogated in T1/ST2-deficient mice. Furthermore, we clearly demonstrate that in the absence of T1/ST2 expression, the levels of Th2 cytokine production are severely impaired after immunization. Thus, in a secondary pulmonary granuloma model, draining lymph node Cells from the T1/ST2-deficient animals produced significantly reduced levels of IL-4 and IL-5, despite developing granulomas of a magnitude similar to those of wild-type mice and comparable antigen-specific immunoglobulin isotype production. These data clearly demonstrate that T1/ST2 expression plays a role in the development of Th2-like cytokine responses and indicate that effector functions are inhibited in its absence.
Sophie M Lehar - One of the best experts on this subject based on the ideXlab platform.
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crucial role of the interleukin 1 receptor family member t1 st2 in t Helper Cell type 2 mediated lung mucosal immune responses
Journal of Experimental Medicine, 1999Co-Authors: Anthony J Coyle, Clare M Lloyd, Jane Tian, Trang Nguyen, Christina Erikkson, Lin Wang, Par Ottoson, Per Persson, Tracy Delaney, Sophie M LeharAbstract:T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T Helper Cell type 2 (Th2), but not Th1 effector Cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 Cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.
Ivan J Fuss - One of the best experts on this subject based on the ideXlab platform.
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specific regulation of t Helper Cell 1 mediated murine colitis by ceacam1
Journal of Experimental Medicine, 2004Co-Authors: Hideki Iijima, Markus F. Neurath, Takashi Nagaishi, Jonathan N Glickman, Edward E S Nieuwenhuis, Atsushi Nakajima, Daohong Chen, Ivan J Fuss, Nalan Utku, Daniel N LewickiAbstract:Carcinoembryonic antigen-related Cellular adhesion molecule 1 (CEACAM1) is a Cell surface molecule that has been proposed to negatively regulate T Cell function. We have shown that CEACAM1 is associated with specific regulation of T Helper Cell (Th)1 pathways, T-bet–mediated Th1 cytokine signaling, and Th1-mediated immunopathology in vivo. Mice treated with anti–mouse CEACAM1-specific monoclonal antibody (mAb) CC1 during the effector phase exhibited a reduced severity of trinitrobenzene sulfonic acid colitis in association with decreased interferon (IFN)-γ production. Although oxazolone colitis has been reported as Th2 mediated, mice treated with the CC1 mAb or a CEACAM1-Fc chimeric protein exhibited a reduced severity of colitis in association with a significant reduction of IFN-γ and T-bet activation, whereas signal transducer and activator of antigen 4 activation was unaffected. Both interleukin-4 and IFN-γ gene–deficient mice exhibited less severe colitis induction by oxazolone. Direct ligation of T Cells in vitro with the murine hepatitis virus spike protein, a natural ligand for the N-domain of CEACAM1, inhibited the differentiation of naive Cells into Th1 but not Th2 Cells and activation of Th1 but not Th2 cytokine production. These results indicate that CEACAM1 isoforms are a novel class of activation-induced Cell surface molecules on T Cells that function in the specific regulation of Th1-mediated inflammation such as that associated with inflammatory bowel disease.
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treatment of experimental trinitrobenzene sulfonic acid colitis by intranasal administration of transforming growth factor tgf β1 plasmid tgf β1 mediated suppression of t Helper Cell type 1 response occurs by interleukin il 10 induction and il 12 rec
Journal of Experimental Medicine, 2000Co-Authors: Atsushi Kitani, Ivan J Fuss, Kazuhiko Nakamura, Owen Schwartz, Takashi Usui, Warren StroberAbstract:In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor β1 (pCMV-TGF-β1) prevents the development of T Helper Cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-β1 protein does not have this effect. Intranasal pCMV-TGF-β1 administration leads to the expression of TGF-β1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-β1–producing T Cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These Cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-γ production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor β2 (IL-12Rβ2) chain expression. Coadministration of anti–IL-10 at the time of pCMV-TGF-β1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-γ secretion. However, anti–IL-10 leads to increased tumor necrosis factor α production, especially in established colitis. Taken together, these studies show that TGF-β1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rβ2 chain expression. In addition, TGF-β1 may also have an inhibitory effect on IFN-γ transcription.
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oxazolone colitis a murine model of t Helper Cell type 2 colitis treatable with antibodies to interleukin 4
Journal of Experimental Medicine, 1998Co-Authors: Monica Boirivant, Ivan J Fuss, Warren StroberAbstract:In this study we describe oxazolone colitis, a new form of experimental colitis. This model is induced in SJL/J mice by the rectal instillation of the haptenating agent, oxazolone, and is characterized by a rapidly developing colitis confined to the distal half of the colon; it consists of a mixed neutrophil/lymphocyte infiltration limited to the superficial layer of the mucosa which is associated with ulceration. Oxazolone colitis is a T Helper Cell type 2 (Th2)-mediated process since stimulated T Cells from lesional tissue produce markedly increased amounts of interleukin (IL)-4 and IL-5; in addition, anti–IL-4 administration leads to a striking amelioration of disease, whereas anti–IL-12 administration either has no effect or exacerbates disease. Finally, this proinflammatory Th2 cytokine response is counterbalanced by a massive transforming growth factor-β (TGF-β) response which limits both the extent and duration of disease: lesional (distal) T Cells manifest a 20–30-fold increase in TGF-β production, whereas nonlesional (proximal) T Cells manifest an even greater 40–50-fold increase. In addition, anti–TGF-β administration leads to more severe inflammation which now involves the entire colon. The histologic features and distribution of oxazolone colitis have characteristics that resemble ulcerative colitis (UC) and thus sharply distinguish this model from most other models, which usually resemble Crohn's disease. This feature of oxazolone colitis as well as its cytokine profile have important implications to the pathogenesis and treatment of UC.
Michael J Townsend - One of the best experts on this subject based on the ideXlab platform.
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t1 st2 deficient mice demonstrate the importance of t1 st2 in developing primary t Helper Cell type 2 responses
Journal of Experimental Medicine, 2000Co-Authors: Michael J Townsend, Padraic G Fallon, David John Matthews, Helen E Jolin, Andrew N J MckenzieAbstract:We have generated mice with a deficiency in T1/ST2 expression to clarify the roles of T1/ST2 in T Helper Cell type 2 (Th2) responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of T1/ST2-deficient mice with those generated by wild-type mice. Using a primary pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that granuloma formation, characterized by eosinophil infiltration, is abrogated in T1/ST2-deficient mice. Furthermore, we clearly demonstrate that in the absence of T1/ST2 expression, the levels of Th2 cytokine production are severely impaired after immunization. Thus, in a secondary pulmonary granuloma model, draining lymph node Cells from the T1/ST2-deficient animals produced significantly reduced levels of IL-4 and IL-5, despite developing granulomas of a magnitude similar to those of wild-type mice and comparable antigen-specific immunoglobulin isotype production. These data clearly demonstrate that T1/ST2 expression plays a role in the development of Th2-like cytokine responses and indicate that effector functions are inhibited in its absence.