Failure of germinal center formation and impairment of response to endotoxin in tumor necrosis factor alpha-deficient mice.
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.
Taniguchi
T
T
Animal Genome Analysis Team, STAFF-Institute, Tsukuba City, Japan.
Takata
M
M
Ikeda
A
A
Momotani
E
E
Sekikawa
K
K
D000818:Animals; D004731:Endotoxins / Q000276:immunology*; D017353:Gene Deletion; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology*; D007109:Immunity / Q000235:genetics*; D008221:Lymphoid Tissue / Q000196:embryology* / Q000276:immunology*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha