B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes.
Upon systemic activation by antigens, CD8(+), but not CD4(+), T cells selectively accumulate and undergo apoptosis in the liver, a mechanism associated with the induction of hepatic tolerance and chronic infection. The molecular basis for CD8(+) T cell preference in this process is unknown. We prepared B7-H1-deficient mice by gene targeting and found spontaneous accumulation of CD8(+) T cells in the liver while CD4(+) T cell levels remained normal. Moreover, antigen-driven CD8(+) T cells proliferated normally while apoptotic levels during the contraction phase was selectively impaired in the liver, leading to accelerated hepatocyte damage in experimental autoimmune hepatitis. Therefore, B7-H1 is a key protein selectively regulating the accumulation and deletion of intrahepatic CD8(+) T cells and may also contribute to inflammation, autoimmune diseases, and tolerance in the liver.
Dong
Haidong
H
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Zhu
Gefeng
G
Tamada
Koji
K
Flies
Dallas B
DB
van Deursen
Jan M A
JM
Chen
Lieping
L
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D060890:B7-H1 Antigen; D001798:Blood Proteins; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement; D006520:Hepatitis, Animal / Q000276:immunology / Q000473:pathology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides