期刊
IMMUNOLOGY LETTERS
卷 126, 期 1-2, 页码 67-72出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2009.08.001
关键词
NOG mice; NOD/Shi-scid IL2r gamma(null) mouse; Human CTL; Tumor immunity
类别
资金
- Ministry of Education, Culture, Sport, Science and Technology (MEXT), Japan [16590988, 17390292, 17015035, 18014023, 19591172, 19059012]
- Ministry of Health, Labour and Welfare,Japan
- Japan Science and Technology Agency (JST)
- Grants-in-Aid for Scientific Research [16590988, 19059012, 17015035, 19591172, 17390292, 18014023] Funding Source: KAKEN
In vivo assay to evaluate anti-cancer immunotherapy at the pre-clinical phase is eagerly needed. We currently established xenotransplantation-based method to analyze in vivo priming of cancer-antigen-specific human cytotoxic T lymphocytes (CTLs). We transplanted human peripheral T cells and analyzed priming of CTLs in NOG mice. Half of the mice engrafted with bulk lymphocytes including CD4(+) T cells died before analysis probably due to xenoreactive graft versus host disease. All of the mice engrafted with purified CD8(+) T cells survived until the analysis, and successful engraftment was observed in 80% of recipient mice. Thus, transfer of purified CD8(+) T cells is sufficient and safer than that of bulk lymphocytes. To add antigenic stimulation to the CD8(+) T cells in vivo, injection of antigenic peptide-loaded and monocyte-derived autologous dendritic cells (DCs) was simultaneously done and repeated 7 days later. The DC-based vaccinization resulted in efficient priming of HLA class I-restricted and MART1, WT1 or CMV peptides-specific CTLs in the recipient mice. This system may be useful to evaluate the stimulation of antigen-specific human CTLs in vivo. (C) 2009 Elsevier B.V. All rights reserved.
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