title: A human memory T cell subset with stem cell-like properties.
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(-), 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.
authors.affiliation: Center for Cancer Research, National Cancer Institute, US National Institutes of Health (NIH), Bethesda, Maryland, USA. gattinol@mail.nih.gov
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Pos
authors.forename: Chrystal M
authors.initials: CM
authors.lastname: Paulos
authors.forename: Máire F
authors.initials: MF
authors.lastname: Quigley
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Almeida
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: Zhiya
authors.initials: Z
authors.lastname: Yu
authors.forename: Carmine
authors.initials: C
authors.lastname: Carpenito
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D019041:L-Selectin / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D054400:Receptors, CCR7 / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; D018106:CD28 Antigens; D054400:Receptors, CCR7; D020395:Receptors, Interleukin-7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C415350:interleukin-7 receptor, alpha chain; D019041:L-Selectin; D017493:Leukocyte Common Antigens