title: Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation.
abstract: Adoptive immunotherapy with functional T cells is potentially an effective therapeutic strategy for combating many types of cancer and viral infection. However, exhaustion of antigen-specific T cells represents a major challenge to this type of approach. In an effort to overcome this problem, we reprogrammed clonally expanded antigen-specific CD8(+) T cells from an HIV-1-infected patient to pluripotency. The T cell-derived induced pluripotent stem cells were then redifferentiated into CD8(+) T cells that had a high proliferative capacity and elongated telomeres. These "rejuvenated" cells possessed antigen-specific killing activity and exhibited T cell receptor gene-rearrangement patterns identical to those of the original T cell clone from the patient. We also found that this method can be effective for generating specific T cells for other pathology-associated antigens. Thus, this type of approach may have broad applications in the field of adoptive immunotherapy.
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Nishimura
authors.forename: Shin
authors.initials: S
authors.lastname: Kaneko
authors.forename: Ai
authors.initials: A
authors.lastname: Kawana-Tachikawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tajima
authors.forename: Haruo
authors.initials: H
authors.lastname: Goto
authors.forename: Dayong
authors.initials: D
authors.lastname: Zhu
authors.forename: Kaori
authors.initials: K
authors.lastname: Nakayama-Hosoya
authors.forename: Shoichi
authors.initials: S
authors.lastname: Iriguchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uemura
authors.forename: Takafumi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Naoya
authors.initials: N
authors.lastname: Takayama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.forename: Ken
authors.initials: K
authors.lastname: Nishimura
authors.forename: Manami
authors.initials: M
authors.lastname: Ohtaka
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Aikichi
authors.initials: A
authors.lastname: Iwamoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Mahito
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Koji
authors.initials: K
authors.lastname: Eto
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism