A human memory T cell subset with stem cell-like properties

Luca Gattinoni, Enrico Lugli, Yun Ji, Zoltan Pos, Chrystal M. Paulos, Máire F. Quigley, Jorge R. Almeida, Emma Gostick, Zhiya Yu, Carmine Carpenito, Ena Wang, Daniel C. Douek, David A. Price, Carl H. June, Francesco M. Marincola, Mario Roederer, Nicholas P. Restifo

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Abstract

Immunological memory is thought to depend on a stem cell-like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T cell population that has an enhanced capacity for self-renewal and a multipotent ability to derive central memory, effector memory and effector T cells. These cells, specific to multiple viral and self-tumor antigens, were found within a CD45RO ĝ̂', CCR7 +, CD45RA +, CD62L +, CD27 +, CD28 + and IL- 7Rα + T cell compartment characteristic of naive T cells. However, they expressed large amounts of CD95, IL-2Rβ, CXCR3, and LFA-1, and showed numerous functional attributes distinctive of memory cells. Compared with known memory populations, these lymphocytes had increased proliferative capacity and more efficiently reconstituted immunodeficient hosts, and they mediated superior antitumor responses in a humanized mouse model. The identification of a human stem cell-like memory T cell population is of direct relevance to the design of vaccines and T cell therapies.

Original languageEnglish
Pages (from-to)1290-1297
Number of pages8
JournalNature Medicine
Volume17
Issue number10
DOIs
Publication statusPublished - 1 Oct 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., Almeida, J. R., Gostick, E., Yu, Z., Carpenito, C., Wang, E., Douek, D. C., Price, D. A., June, C. H., Marincola, F. M., Roederer, M., & Restifo, N. P. (2011). A human memory T cell subset with stem cell-like properties. Nature Medicine, 17(10), 1290-1297. https://doi.org/10.1038/nm.2446