Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation
Toshinobu Nishimura, Shin Kaneko, Ai Kawana-Tachikawa, Yoko Tajima, Haruo Goto, Dayong Zhu, Kaori Nakayama-Hosoya, Shoichi Iriguchi, Yasushi Uemura, Takafumi Shimizu, Naoya Takayama, Daisuke Yamada, Ken Nishimura, Manami Ohtaka, Nobukazu Watanabe, Satoshi Takahashi, Aikichi Iwamoto, Haruhiko Koseki, Mahito Nakanishi, Koji Eto, Hiromitsu Nakauchi, Toshinobu Nishimura, Shin Kaneko, Ai Kawana-Tachikawa, Yoko Tajima, Haruo Goto, Dayong Zhu, Kaori Nakayama-Hosoya, Shoichi Iriguchi, Yasushi Uemura, Takafumi Shimizu, Naoya Takayama, Daisuke Yamada, Ken Nishimura, Manami Ohtaka, Nobukazu Watanabe, Satoshi Takahashi, Aikichi Iwamoto, Haruhiko Koseki, Mahito Nakanishi, Koji Eto, Hiromitsu Nakauchi
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Source: PubMed