Fas-mediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graft-versus-host disease in mice

T. Sakai, Y. Kimura, K. Inagaki-Ohara, K. Kusugami, D. H. Lynch, Yasunobu Yoshikai

    Research output: Contribution to journalArticle

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    Abstract

    Background and Aims: Host-derived intestinal intraepithelial lymphocytes (IELs) increase in number during acute graft-versus-host disease (GVHD) in mice. In the present study, we examined Fas-mediated cytotoxicity by host- derived IELs against Fas-expressing target cells to see whether Fas/Fas ligand (Fas-L) interaction is involved in the pathogenesis of enteropathy during acute GVHD. Methods: Acute GVHD was induced by injection of parental spleen cells into nonirradiated F1 mice. The expression of Fas antigen on the intestinal epithelial cells (IECs) was examined by flow cytometry, and the expression of messenger RNA (mRNA) for Fas-L, interleukin 2, and interferon gamma in host-derived IELs was assessed by reverse-transcription polymerase chain reaction. Fas-mediated cytotoxicity by host-derived IELs was assessed using Fas-transfected cells, IECs, and Fas immunoglobulin Fc fusion protein (Fas Fc). Results: Fas antigen was constitutively expressed on the cell surface of IECs before and after GVHD induction. Although Fas-L mRNA was not detected or detected scarcely in either αβ or γδ IELs before GVHD induction, both IELs expressed high levels of mRNA for Fas-L and interferon gamma after GVHD induction. Host-derived IELs during acute GVHD showed cytotoxicity against Fas-transfected target cells and IECs, which was partly blocked by addition of Fas Fc. Conclusions: Fas/Fa-L-mediated cytotoxicity by host-derived IELs may be partly responsible for the enteropathy during acute GVHD.

    Original languageEnglish
    Pages (from-to)168-174
    Number of pages7
    JournalGastroenterology
    Volume113
    Issue number1
    DOIs
    Publication statusPublished - Jan 1 1997

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    Graft vs Host Disease
    Lymphocytes
    Fas Ligand Protein
    Epithelial Cells
    CD95 Antigens
    Messenger RNA
    Interferon-gamma
    Immunoglobulin Fc Fragments
    Reverse Transcription
    Interleukin-2
    Flow Cytometry
    Spleen
    Polymerase Chain Reaction
    Injections

    All Science Journal Classification (ASJC) codes

    • Hepatology
    • Gastroenterology

    Cite this

    Fas-mediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graft-versus-host disease in mice. / Sakai, T.; Kimura, Y.; Inagaki-Ohara, K.; Kusugami, K.; Lynch, D. H.; Yoshikai, Yasunobu.

    In: Gastroenterology, Vol. 113, No. 1, 01.01.1997, p. 168-174.

    Research output: Contribution to journalArticle

    Sakai, T, Kimura, Y, Inagaki-Ohara, K, Kusugami, K, Lynch, DH & Yoshikai, Y 1997, 'Fas-mediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graft-versus-host disease in mice', Gastroenterology, vol. 113, no. 1, pp. 168-174. https://doi.org/10.1016/S0016-5085(97)70092-1
    Sakai, T. ; Kimura, Y. ; Inagaki-Ohara, K. ; Kusugami, K. ; Lynch, D. H. ; Yoshikai, Yasunobu. / Fas-mediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graft-versus-host disease in mice. In: Gastroenterology. 1997 ; Vol. 113, No. 1. pp. 168-174.
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    abstract = "Background and Aims: Host-derived intestinal intraepithelial lymphocytes (IELs) increase in number during acute graft-versus-host disease (GVHD) in mice. In the present study, we examined Fas-mediated cytotoxicity by host- derived IELs against Fas-expressing target cells to see whether Fas/Fas ligand (Fas-L) interaction is involved in the pathogenesis of enteropathy during acute GVHD. Methods: Acute GVHD was induced by injection of parental spleen cells into nonirradiated F1 mice. The expression of Fas antigen on the intestinal epithelial cells (IECs) was examined by flow cytometry, and the expression of messenger RNA (mRNA) for Fas-L, interleukin 2, and interferon gamma in host-derived IELs was assessed by reverse-transcription polymerase chain reaction. Fas-mediated cytotoxicity by host-derived IELs was assessed using Fas-transfected cells, IECs, and Fas immunoglobulin Fc fusion protein (Fas Fc). Results: Fas antigen was constitutively expressed on the cell surface of IECs before and after GVHD induction. Although Fas-L mRNA was not detected or detected scarcely in either αβ or γδ IELs before GVHD induction, both IELs expressed high levels of mRNA for Fas-L and interferon gamma after GVHD induction. Host-derived IELs during acute GVHD showed cytotoxicity against Fas-transfected target cells and IECs, which was partly blocked by addition of Fas Fc. Conclusions: Fas/Fa-L-mediated cytotoxicity by host-derived IELs may be partly responsible for the enteropathy during acute GVHD.",
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    AU - Lynch, D. H.

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    N2 - Background and Aims: Host-derived intestinal intraepithelial lymphocytes (IELs) increase in number during acute graft-versus-host disease (GVHD) in mice. In the present study, we examined Fas-mediated cytotoxicity by host- derived IELs against Fas-expressing target cells to see whether Fas/Fas ligand (Fas-L) interaction is involved in the pathogenesis of enteropathy during acute GVHD. Methods: Acute GVHD was induced by injection of parental spleen cells into nonirradiated F1 mice. The expression of Fas antigen on the intestinal epithelial cells (IECs) was examined by flow cytometry, and the expression of messenger RNA (mRNA) for Fas-L, interleukin 2, and interferon gamma in host-derived IELs was assessed by reverse-transcription polymerase chain reaction. Fas-mediated cytotoxicity by host-derived IELs was assessed using Fas-transfected cells, IECs, and Fas immunoglobulin Fc fusion protein (Fas Fc). Results: Fas antigen was constitutively expressed on the cell surface of IECs before and after GVHD induction. Although Fas-L mRNA was not detected or detected scarcely in either αβ or γδ IELs before GVHD induction, both IELs expressed high levels of mRNA for Fas-L and interferon gamma after GVHD induction. Host-derived IELs during acute GVHD showed cytotoxicity against Fas-transfected target cells and IECs, which was partly blocked by addition of Fas Fc. Conclusions: Fas/Fa-L-mediated cytotoxicity by host-derived IELs may be partly responsible for the enteropathy during acute GVHD.

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