International Immunology, Vol 9, 307-316, Copyright © 1997 by Oxford University Press
Y Nishimura, Y Hirabayashi, Y Matsuzaki, P Musette, A Ishii, H Nakauchi, T Inoue and S Yonehara
Fas antigen (Fas/CD95) is a cell surface receptor protein that mediates
apoptosis-inducing signals. To analyze the function of Fas in vivo, we
examined the effects of agonistic anti-Fas antibodies in mice. The i.p.
administration of the hamster anti-mouse Fas mAb, RK-8, which induced
apoptosis both in vivo and in vitro, did not kill adult mice, whereas those
given the another hamster anti-mouse Fas mAb, Jo2, rapidly died of
fulminant hepatitis with hemorrhage. Histological analyses of mice given
RK-8 indicated severe damage of the thymus, and moderate damage of the
spleen and liver. Most of the thymocytes and some hepatocytes underwent
apoptosis within 1 day of administration. Flow cytometry revealed that CD4+
T cells were more sensitive to Fas-mediated apoptosis than CD8+ T cells. At
day 7 after administration, the thymus was atrophied. These in vivo effects
of RK-8 were transient; the thymus was regenerated, and the liver and
spleen were apparently normal 1 month after injection. The administration
of RK-8 into newborn mice caused severe damage of the liver and thymus.
Most of the hepatocytes died and jaundice was induced. The newborn mice
died within 1 week. Most hepatocytes of newborn mice may be more sensitive
to apoptosis- inducing signals through Fas than those of adult mice. These
results indicated that functional Fas, which introduces the death signal in
vivo, is expressed on thymocytes, CD4+ splenocytes, and some adult and most
newborn mouse hepatocytes.
ARTICLES
In vivo analysis of Fas antigen-mediated apoptosis: effects of agonistic anti-mouse Fas mAb on thymus, spleen and liver
The Pharmaceutical Basic Research Laboratories, JT Inc., Yokohama, Japan.
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