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Nat Immunol. 2013 Jun;14(6):603-10. doi: 10.1038/ni.2606. Epub 2013 May 5.

T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion.

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Swiss Vaccine Research Institute, Epalinges, Switzerland.


During chronic infection, pathogen-specific CD8(+) T cells upregulate expression of molecules such as the inhibitory surface receptor PD-1, have diminished cytokine production and are thought to undergo terminal differentiation into exhausted cells. Here we found that T cells with memory-like properties were generated during chronic infection. After transfer into naive mice, these cells robustly proliferated and controlled a viral infection. The reexpanded T cell populations continued to have the exhausted phenotype they acquired during the chronic infection. Thus, the cells underwent a form of differentiation that was stably transmitted to daughter cells. We therefore propose that during persistent infection, effector T cells stably differentiate into a state that is optimized to limit viral replication without causing overwhelming immunological pathology.

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