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Superior T memory stem cell persistence supports long-lived T cell memory

Lugli, Enrico, Dominguez, Maria H., Gattinoni, Luca, Chattopadhyay, Pratip K., Bolton, Diane L., Song, Kaimei, Klatt, Nichole R., Brenchley, Jason M., Vaccari, Monica, Gostick, Emma, Price, David, Waldmann, Thomas A., Restifo, Nicholas P., Franchini, Genoveffa and Roederer, Mario 2013. Superior T memory stem cell persistence supports long-lived T cell memory. The Journal of Clinical Investigation 123 (2) , pp. 594-599. 10.1172/JCI66327

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Long-lived memory T cells are able to persist in the host in the absence of antigen; however, the mechanism by which they are maintained is not well understood. Recently, a subset of human T cells, stem cell memory T cells (TSCM cells), was shown to be self-renewing and multipotent, thereby providing a potential reservoir for T cell memory throughout life. However, their in vivo dynamics and homeostasis still remain to be defined due to the lack of suitable animal models. We identified T cells with a TSCM phenotype and stem cell–like properties in nonhuman primates. These cells were the least-differentiated memory subset, were functionally distinct from conventional memory cells, and served as precursors of central memory. Antigen-specific TSCM cells preferentially localized to LNs and were virtually absent from mucosal surfaces. They were generated in the acute phase of viral infection, preferentially survived in comparison with all other memory cells following elimination of antigen, and stably persisted for the long term. Thus, one mechanism for maintenance of long-term T cell memory derives from the unique homeostatic properties of TSCM cells. Vaccination strategies designed to elicit durable cellular immunity should target the generation of TSCM cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR180 Immunology
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Date of First Compliant Deposit: 1 April 2016
Date of Acceptance: 1 November 2012
Last Modified: 13 Oct 2017 15:17

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