Generation of Rejuvenated Antigen-Specific T Cells by Reprogramming to Pluripotency and Redifferentiation

被引：292

作者：

Nishimura, Toshinobu ^{[1
]}

Kaneko, Shin ^{[1
]}

Kawana-Tachikawa, Ai ^{[2
]}

Tajima, Yoko ^{[1
]}

Goto, Haruo ^{[1
]}

Zhu, Dayong ^{[2
]}

Nakayama-Hosoya, Kaori ^{[2
]}

Iriguchi, Shoichi ^{[1
]}

Uemura, Yasushi ^{[6
]}

Shimizu, Takafumi ^{[1
]}

Takayama, Naoya ^{[3
]}

Yamada, Daisuke ^{[7
]}

Nishimura, Ken ^{[8
]}

Ohtaka, Manami ^{[8
]}

Watanabe, Nobukazu ^{[4
]}

Takahashi, Satoshi ^{[5
]}

Iwamoto, Aikichi ^{[2
]}

Koseki, Haruhiko ^{[7
]}

Nakanishi, Mahito ^{[8
]}

Eto, Koji ^{[3
]}

Nakauchi, Hiromitsu ^{[1
]}

机构：

[1] Univ Tokyo, Div Stem Cell Therapy, Ctr Stem Cell Biol & Regenerat Med, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[2] Univ Tokyo, Div Infect Dis, Adv Clin Res Ctr, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[3] Univ Tokyo, Stem Cell Bank, Ctr Stem Cell Biol & Regenerat Med, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[4] Univ Tokyo, Lab Diagnost Med, Ctr Stem Cell Biol & Regenerat Med, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[5] Univ Tokyo, Div Mol Therapy, Adv Clin Res Ctr, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[6] Aichi Canc Ctr, Div Immunol, Res Inst, Chikusa Ku, Nagoya, Aichi 4648681, Japan

[7] RIKEN Ctr Allergy & Immunol, Lab Lymphocyte Dev, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[8] Natl Inst Adv Ind Sci & Technol, Res Ctr Stem Cell Engn, Tsukuba, Ibaraki 3058562, Japan

来源：

CELL STEM CELL | 2013年 / 12卷 / 01期

基金：

日本学术振兴会;

关键词：

EMBRYONIC STEM-CELLS; HUMAN PERIPHERAL-BLOOD; GENE-THERAPY; TELOMERE LENGTH; SUICIDE GENE; IN-VITRO; MATURE B; MEMORY; IMMUNODEFICIENCY; VIRUS;

D O I：

10.1016/j.stem.2012.11.002

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：114 / 126

页数：13

共 68 条

[1] JOINING OF IMMUNOGLOBULIN HEAVY-CHAIN GENE SEGMENTS - IMPLICATIONS FROM A CHROMOSOME WITH EVIDENCE OF 3 D-JH FUSIONS [J].