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Lab Invest. 1997 Dec;77(6):647-58.

Failure of germinal center formation and impairment of response to endotoxin in tumor necrosis factor alpha-deficient mice.

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Animal Genome Analysis Team, STAFF-Institute, Tsukuba City, Japan.


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.

[Indexed for MEDLINE]

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