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Centenary Institute - Medical Research
Centenary Institute - Medical Research

Hepatocyte entry leads to degradation of autoreactive CD8 T cells.

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 ofautoreactive T-cell deletion, a process critical for the maintenance of tolerance.

Benseler V, Warren A, Vo M, Holz L, Tay SS, Le Couteur DG, Breen E, Allison A, van Rooijen N, McGuffog C, Schlitt HJ, Bowen DG, McCaughan GW and Bertolino P.

Proc. Natl. Acad. Sci. USA, 108, 16735-16740 (IF: 9.8). (2011)

Date: 2011