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Failure
of Germinal Center Formation and Impairment of Response to Endotoxin in
Tumor Necrosis Factor [alpha]-Deficient Mice |
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Takahide Taniguchi,
Masuhiro Takata, Akemi Ikeda, Eiichi Momotani, and Kenji Sekikawa
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Animal
Genome Analysis Team (TT, AI), STAFF-Institute, and Department of Immunology
(MT, EM, KS), National Institute of Animal Health, Tsukuba City, Japan |
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To study the pathophysiologic
roles of TNF[alpha], we produced TNF[alpha] gene-disrupted mice by gene
targeting. TNF[alpha]-deficient mice develop normally without any alteration
in the lymphocyte populations. However, in these mice, the germinal center
formation in the peripheral lymphoid organs failed in response to the T
cell-dependent antigens. TNF[alpha]-deficient mice are resistant to lethal
doses of endotoxin and d-galactosamine without hepatocyte apoptosis, yet
demonstrate thymus apoptosis. Our results indicated an important role for
TNF[alpha] in germinal center formation and in the sepsis-induced hepatocyte
apoptosis that precedes liver failure. |
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