title: Identification of a novel human memory T-cell population with the characteristics of stem-like chemo-resistance.
abstract: High-dose chemotherapy may kill not only tumor cells but also immunocytes, and frequently induces severe lymphocytopenia. On the other hand, patients who recover from the nadir maintain immunity against infection, suggesting the existence of an unknown memory T-cell population with stress resistance, long-living capacity, proliferation and differentiation. Recently, the differentiation system of T-cell memory has been clarified using mouse models. However, the human T-cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. Here we report a novel human T-cell memory population, "young memory" T (TYM) cells. TYM cells are defined by positive expression of CD73, which represents high aldehyde dehydrogenase 1 (ALDH1) activity and CXCR3 among CD8(+)CD45RA(+)CD62L(+) T cells. TYM proliferate upon TCR stimulation, with differentiation capacity into TCM and TEM and drug resistance. Moreover, TYM are involved in memory function for viral and tumor-associated antigens in healthy donors and cancer patients, respectively. Regulation of TYM might be very attractive for peptide vaccination, adoptive cell-transfer therapy and hematopoietic stem cell transplantation.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan; Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Emori
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan; Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shibayama
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan; Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Mizushima
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumiya
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kaya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.affiliation: Department of Human Immunology, Research Institute of Frontier Medicine, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine , Chuo-ku, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
keywords: Adoptive cell transfer; memory T stem cell; peptide vaccine; tumor-associated antigen; viral antigen