Hepatocyte entry leads to degradation of autoreactive CD8 T cells.
Proc Natl Acad Sci U S A
; 108(40): 16735-40, 2011 Oct 04.
Article
em En
| MEDLINE
| ID: mdl-21933957
ABSTRACT
Although most self-reactive T cells are eliminated in the thymus, mechanisms to inactivate or control T cells specific for extrathymic antigens are required and exist in the periphery. By investigating the site in which autoreactive T cells are tolerized, we identify a unique mechanism of peripheral deletion in which naïve autoreactive CD8 T cells are rapidly eliminated in the liver after intrahepatic activation. T cells actively invade hepatocytes, enter endosomal/lysosomal compartments, and are degraded. Blockade of this process leads to accumulation of autoreactive CD8 T cells in the liver and breach of tolerance, with the development of autoimmune hepatitis. Cell into cell invasion, or emperipolesis, is a long-observed phenomenon for which a physiological role has not been previously demonstrated. We propose that this "suicidal emperipolesis" is a unique mechanism of autoreactive T-cell deletion, a process critical for the maintenance of tolerance.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Morte Celular
/
Linfócitos T CD8-Positivos
/
Hepatócitos
/
Emperipolese
/
Tolerância Periférica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article