Benseler, Volker and Warren, Alessandra and Vo, Michelle and Holz, Lauren E. and Tay, Szun S. and Le Couteur, David G. and Breen, Eamon and Allison, Anthony C. and van Rooijen, Nico and McGuffog, Claire and Schlitt, Hans J. and Bowen, David G. and McCaughan, Geoffrey W. and Bertolino, Patrick (2011) Hepatocyte entry leads to degradation of autoreactive CD8 T cells. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108 (40). pp. 16735-16740. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)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 naive 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THYMIC NURSE CELLS; BONE-MARROW; LIVER; LYMPHOCYTES; ACTIVATION; HEPATITIS; TOLERANCE; MECHANISM; RESPONSES; transgenic mice transplantation; hepatitis C virus; cell-in cell; cannibalism; entosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 May 2020 05:55 |
| Last Modified: | 28 May 2020 05:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19987 |
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