Reference - Detail
|Author||Tajima M, Wakita D, Satoh T, Kitamura H, Nishimura T.|
|Title||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.
|MeSH||Animals CD8-Positive T-Lymphocytes / drug effects* CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / pathology Cancer Vaccines Cell Differentiation / drug effects Cell Line, Tumor Cytotoxicity, Immunologic* Interferon-gamma / metabolism Interleukin-12 / pharmacology Interleukin-17 / genetics Interleukin-17 / metabolism* Leukemia, T-Cell / immunology* Leukemia, T-Cell / pathology Leukemia, T-Cell / therapy Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Skin Neoplasms / immunology* Skin Neoplasms / pathology Skin Neoplasms / therapy T-Lymphocyte Subsets / drug effects* T-Lymphocyte Subsets / immunology T-Lymphocyte Subsets / metabolism T-Lymphocyte Subsets / pathology Tumor Burden|