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Potential
for Involvement of Fas Antigen/Fas Ligand Interaction in Apoptosis of Epithelial
Cells by Intraepithelial Lymphocytes in Murine Small Intestine |
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Kyoko Inagaki-Ohara,
Hitoshi Nishimura, Tetsu Sakai, David H. Lynch, and Yasunobu Yoshikai
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Laboratory
of Host Defense and Germfree Life (KIO, HN, TS, YY), Research Institute
for Disease Mechanism and Control, Nagoya University School of Medicine,
Nagoya, Japan; and Department of Immunobiology (DHL), Immunex Research and
Development Corporation, Seattle, Washington |
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Intestinal epithelial cells
(i-EC), which move to the villus tips from the crypts, rapidly die by apoptosis
at the villus tips and are perpetually renewed at the crypts. To determine
whether the Fas antigen (Fas)/Fas ligand (FasL) system is involved in the
mechanism leading to apoptosis of i-EC, we examined the expression of Fas
and FasL on the i-EC and intestinal intraepithelial lymphocytes (i-IEL)
in normal mice. A high level of Fas was expressed on both the i-EC and i-IEL,
whereas FasL was expressed in the i-IEL, especially in high-density fraction
upon separation (high-density i-IEL), but not in the i-EC. The high-density
i-IEL exhibited cytotoxicity against not only Fas transfectant but also
the i-EC, and the cytotoxicity was inhibited by addition of Fas-Fragment
c chimeric fusion protein. Thus, a significant fraction of i-IEL, such as
high-density i-IEL, may partly contribute to induction of apoptosis in the
effete i-EC via Fas/FasL interaction. |
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