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         headline:A human memory T cell subset with stem cell–like properties
         description:Whether there exists a human memory T cell population with stem cell–like properties of self-renewal and multipotency is under active investigation. Here Gattinoni et al. characterize a subset of human T cells that phenotypically resemble naive T cells yet have properties associated with memory T cells. These T cells show enhanced ability to self renew and to give rise to differentiated memory cell subsets, suggesting a stem cell–like functionality. 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.
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      headline:A human memory T cell subset with stem cell–like properties
      description:Whether there exists a human memory T cell population with stem cell–like properties of self-renewal and multipotency is under active investigation. Here Gattinoni et al. characterize a subset of human T cells that phenotypically resemble naive T cells yet have properties associated with memory T cells. These T cells show enhanced ability to self renew and to give rise to differentiated memory cell subsets, suggesting a stem cell–like functionality. 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.
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         Metabolic Diseases
         Infectious Diseases
         Molecular Medicine
         Neurosciences
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            address:
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            address:
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      name:Mario Roederer
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            address:
               name:ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, USA
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            address:
               name:Center for Cancer Research, National Cancer Institute, US National Institutes of Health (NIH), Bethesda, USA
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      name:ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, USA
      name:Center for Cancer Research, National Cancer Institute, US National Institutes of Health (NIH), Bethesda, USA
      name:Department of Transfusion Medicine, Infectious Disease and Immunogenetics Section, Clinical Center, US National Institutes of Health, Bethesda, USA
      name:Center for Human Immunology, US National Institutes of Health, Bethesda, USA
      name:Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, USA
      name:Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA
      name:Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Heath Park, Cardiff, UK
      name:Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, USA
      name:Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, USA
      name:Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Heath Park, Cardiff, UK
      name:Center for Cancer Research, National Cancer Institute, US National Institutes of Health (NIH), Bethesda, USA
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