Authors:
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
Summary:
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.
Source:
Cell Stem Cell; Vol. 12, Issue 1, 114-126 (01/03/13)