Enhanced and accelerated lymphoproliferation in Fas-null mice.
Fas is a 45-kDa membrane protein that transduces an apoptotic signal. The mouse lymphoproliferation (lpr) mutation is a leaky mutation of Fas. In this study, we examined lymphocyte development in Fas-null mice generated by gene targeting. The Fas-/- mice progressively accumulated abnormal T cells (Thy1+, B220+, CD4-, and CD8-) and developed lymphadenopathy and splenomegaly, which were much more accelerated and pronounced than those in lpr mice. In addition, the Fas-null mice showed lymphocytosis, accompanied by lymphocytic infiltration in the lungs and liver. The number of apparently normal B cells also increased, and large amounts of immunoglobulins, including anti-DNA antibodies, were produced. Thymic clonal deletion, assessed by deletion of T cells reactive to mouse endogenous superantigens, was apparently normal in the Fas-/- mice, whereas the peripheral clonal deletion of mature T cells against a bacterial superantigen was impaired. These results suggested that Fas plays a decisive role in peripheral clonal deletion but not in negative selection in the thymus.
Adachi
M
M
Osaka Bioscience Institute, Japan.
Suematsu
S
S
Suda
T
T
Watanabe
D
D
Fukuyama
H
H
Ogasawara
J
J
Tanaka
T
T
Yoshida
N
N
Nagata
S
S
D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology; D002455:Cell Division; D017637:Clonal Deletion; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008218:Lymphocytosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D019014:fas Receptor / Q000502:physiology*
D001324:Autoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D019014:fas Receptor