An in vivo model of priming of antigen-specific human CTL by Mo-DC in NOD/Shi-scid IL2rgamma(null) (NOG) mice.
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.
Inoue
Mitsuhiro
M
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan.
Senju
Satoru
S
Hirata
Shinya
S
Irie
Atsushi
A
Baba
Hideo
H
Nishimura
Yasuharu
Y
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D017690:Cell Transplantation; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D005434:Flow Cytometry; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism*; D058965:MART-1 Antigen; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D023421:Models, Animal; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014183:Transplantation, Heterologous
D000941:Antigens; D000951:Antigens, Neoplasm; D019002:CD56 Antigen; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins