CD8 alpha-deficient mice are highly susceptible to 5-fluorouracil-induced lethality.
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 beta 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.
Itoh
Naoto
N
Laboratory of Host Defense, Research Institute for Disease Mechanisms and Control, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Nishimura
Hitoshi
H
Matsuguchi
Tetsuya
T
Yajima
Toshiki
T
Mokuno
Yasuji
Y
Hiromatsu
Takashi
T
Nimura
Yuji
Y
Yoshikai
Yasunobu
Y
D019264:Adoptive Transfer; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000633:toxicity*; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004198:Disease Susceptibility; D004755:Enterobacteriaceae / Q000276:immunology; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000382:microbiology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000382:microbiology
D000963:Antimetabolites; D016827:CD8 Antigens; C431698:CD8alpha antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma; D005472:Fluorouracil