Lymphotoxin activates hepatic T cells and simultaneously induces profound thymic atrophy.
We have recently demonstrated that the liver may be a major site of extrathymic T-cell differentiation. This hepatic pathway was shown to be activated in mice injected with heat-killed bacteria. It is conceivable that the resulting activation of macrophages or lymphocytes, and the production of cytokines may be responsible for a subsequent activation of hepatic T cells. In this context, we investigated the possibility of whether certain cytokines may activate hepatic T cells. It was demonstrated that the administration of lymphotoxin [tumour necrosis factor-beta (TNF-beta)] more than doubled the number of hepatic mononuclear cells (MNC) yielded 3-5 days after the treatment. More strikingly, such treatment induced profound thymic atrophy and resulted in a decrease of more than 95% in the number of thymocytes. Spontaneous proliferation in an in vitro culture of hepatic MNC from treated mice increased, and inversely such activity of thymocytes decreased. The increased number of hepatic MNC was mainly due to an increase in intermediate alpha beta T-cell receptor (TcR) cells, which are extrathymic T cells uniquely seen in the liver. On the other hand, the thymic atrophy was caused by the prompt apoptotic death of dull alpha beta TcR cells with double-positive (DP) CD4+ CD8+ phenotype. These results indicate that lymphotoxin may be one of the factors that activates extrathymic T cells in the liver and at the same time inhibits intrathymic T-cell differentiation.
Kusumi
A
A
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
Abo
T
T
Masuda
T
T
Sugiura
K
K
Seki
S
S
Ohteki
T
T
Okuyama
R
R
Kumagai
K
K
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001284:Atrophy / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D007700:Kinetics; D007958:Leukocyte Count; D008099:Liver / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*
D000954:Antigens, Surface; D008233:Lymphotoxin-alpha