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Clinical and Diagnostic Laboratory Immunology, May 2002, p. 550-557, Vol. 9, No. 3
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.3.550-557.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

CD8{alpha}-Deficient Mice Are Highly Susceptible to 5-Fluorouracil-Induced Lethality

Naoto Itoh,1,2 Hitoshi Nishimura,1 Tetsuya Matsuguchi,1 Toshiki Yajima,1 Yasuji Mokuno,1,2 Takashi Hiromatsu,1,2 Yuji Nimura,2 and Yasunobu Yoshikai1*

Laboratory of Host Defense, Research Institute for Disease Mechanisms and Control,1 Division of Surgical Oncology, Department of Surgery, Nagoya University School of Medicine, Nagoya 466-8550, Japan2

Received 10 September 2001/ Returned for modification 8 November 2001/ Accepted 24 January 2002

Intestinal intraepithelial lymphocytes (i-IEL) expressing CD8{alpha} are located in the intestine and may confer protection against invasion of intestinal microflora. We found that mice rendered deficient in CD8{alpha} molecules by homologous recombination were susceptible to 5-fluorouracil (5-FU)-induced lethality accompanied by translocation of members of the enterobacteria. The number of i-IEL was greatly reduced on day 6 after 5-FU administration in both CD8{alpha}+/- mice and CD8{alpha}-/- mice, whereas the recovery of the level of i-IEL thereafter was significantly impaired in CD8{alpha}-/- mice compared with that in CD8{alpha}+/- mice. The ability of i-IEL to produce gamma interferon in response to immobilized T-cell receptor (TCR) {alpha}ß or TCR {gamma}{delta} monoclonal antibodies was significantly lower in CD8{alpha}-/- mice than in CD8{alpha}+/- mice. Transfer of CD8+ i-IEL conferred significant protection against 5-FU-induced lethality in CD8{alpha}-/- mice. The results suggest that CD8+ i-IEL play an important role in protection against 5-FU-induced lethality with translocation of Enterobacteriaceae.

* Corresponding author. Mailing address: Laboratory of Host Defense, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Phone: 81-52-744-2446. Fax: 81-52-744-2449. E-mail: yyoshika{at}med.nagoya-u.ac.jp.

Clinical and Diagnostic Laboratory Immunology, May 2002, p. 550-557, Vol. 9, No. 3
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.3.550-557.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kim, J-K, Takeuchi, M, Yokota, Y (2004). Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice. Gut 53: 480-486 [Abstract] [Full Text]  


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