Murine Ileitis After Intracellular Parasite Infection Is Controlled by TGF-B Producing Intraepithelial Lymphocytes

BUZONI?GATEL, DOMINIQUE; DEBBABI, HAJER; MENNECHET, FRANCK JD; MARTIN, VALENTINA; LEPAGE, ANNE C; SCHWARTZMAN, JOSEPH D; KASPER, LH

GASTROENTEROLOGY

Año: 2001 vol. 120 p. 914 - 924

0016-5085

Background & Aims: Acute inßammatory ileitis occurs in susceptible (C57BL/6) mice after oral infection withAcute inßammatory ileitis occurs in susceptible (C57BL/6) mice after oral infection with Toxoplasma gondii. Overproduction of interferon (IFN)-g. Overproduction of interferon (IFN)-g and synthesis of nitric oxide mediate the inßammation. We evaluated the role of transforming growth factor (TGF)-b produced by intraepithelial lymphocytes (IELs) in this process. Methods: We analyzed the histologic and immunologic consequences of adoptive transfer of antigen- primed IELs into susceptible mice treated with anti-TGF-b before oral challenge with T. gondii cysts. An in vitro coculture of enterocytes and IELs assessed the production of chemokines and cytokines in the presence of anti-TGF-b. Results: Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-b. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-b. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-g production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromb produced by intraepithelial lymphocytes (IELs) in this process. Methods: We analyzed the histologic and immunologic consequences of adoptive transfer of antigen- primed IELs into susceptible mice treated with anti-TGF-b before oral challenge with T. gondii cysts. An in vitro coculture of enterocytes and IELs assessed the production of chemokines and cytokines in the presence of anti-TGF-b. Results: Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-b. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-b. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-g production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromMethods: We analyzed the histologic and immunologic consequences of adoptive transfer of antigen- primed IELs into susceptible mice treated with anti-TGF-b before oral challenge with T. gondii cysts. An in vitro coculture of enterocytes and IELs assessed the production of chemokines and cytokines in the presence of anti-TGF-b. Results: Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-b. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-b. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-g production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromb before oral challenge with T. gondii cysts. An in vitro coculture of enterocytes and IELs assessed the production of chemokines and cytokines in the presence of anti-TGF-b. Results: Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-b. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-b. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-g production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromb. Results: Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-b. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-b. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-g production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromb. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-b. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-g production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromb. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-g production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromg production. In vitro, primed IELs reduce the production of inßammatory chemokines by infected enterocytes and IFN-g by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting fromg by splenocytes. Conclusions: Regulation of the ileal inßammatory process resulting from T. gondii is dependent on TGF-b-producing IELs. The IELs are an essential component in gut homeostasis after oral infection with this parasite.is dependent on TGF-b-producing IELs. The IELs are an essential component in gut homeostasis after oral infection with this parasite.