IL-17/IFN-γ double producing CD8+ T (Tc17/IFN-γ) cells: a novel cytotoxic T-cell subset converted from Tc17 cells by IL-12.
It has been reported that IFN-γ-producing CD8(+) T (Tc1) cells express cytotoxic molecules such as perforin and granzyme B to exhibit higher cytotoxicity against tumor cells compared with Tc2 cells. However, the critical role of IL-17-producing CD8(+) T (Tc17)-cell subsets in tumor immunity remains unclear. Tc17 cells differentiated from naive CD8(+) T cells did not possess cytotoxic molecules and exhibited no strong cytotoxicity. However, when Tc17 effector cells were further cultured with IL-12, they converted into IFN-γ-producing Tc17 cells, which mainly consisted of IL-17/IFN-γ double-producing cells (Tc17/IFN-γ). IL-12-converted Tc17 cells also acquired cytotoxic function in addition to IFN-γ producibility. Moreover, they showed strong anti-tumor activity both in vitro and in vivo as well as Tc1 cells. Among four distinct subsets in IL-12-converted Tc17 cell populations, the isolated Tc17/IFN-γ cells exhibited cytotoxicity as well as IFN-γ-producing Tc1-like cells. Thus, we first indicate direct evidence that Tc17/IFN-γ cells, which were plastically converted from non-cytotoxic Tc17 cells by IL-12, exhibited strong anti-tumor activity as well as Tc17 cell-derived Tc1-like cells.
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0185, Japan.
Masaki
M
Tajima
Daiko
D
Wakita
Takayuki
T
Satoh
Hidemitsu
H
Kitamura
Takashi
T
Nishimura
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden
D019496:Cancer Vaccines; D020381:Interleukin-17; D018664:Interleukin-12; D007371:Interferon-gamma