title: CD8(+)NKT-like cells regulate the immune response by killing antigen-bearing DCs.
abstract: CD1d-dependent NKT cells have been extensively studied; however, the function of CD8(+)NKT-like cells, which are CD1d-independent T cells with NK markers, remains unknown. Here, we report that CD1d-independent CD8(+)NKT-like cells, which express both T cell markers (TCRβ and CD3) and NK cell receptors (NK1.1, CD49b and NKG2D), are activated and significantly expanded in mice immunized with GFP-expressing dendritic cells. Distinct from CD1d-dependent NKT cells, CD8(+)NKT-like cells possess a diverse repertoire of TCRs and secrete high levels of IFN-gamma but not IL-4. CD8(+)NKT-like cell development is normal in CD1d(-/-) mice, which suggests that CD8(+)NKT-like cells undergo a unique development pathway that differs from iNKT cells. Further functional analyses show that CD8(+)NKT-like cells suppress T-cell responses through elimination of dendritic cells in an antigen-specific manner. Adoptive transfer of antigen-specific CD8(+)NKT-like cells into RIP-OVA mice prevented subsequent development of diabetes in the animals induced by activated OT-I CD8 T cells. Our study suggests that CD8(+)NKT-like cells can function as antigen-specific suppressive cells to regulate the immune response through killing antigen-bearing DCs. Antigen-specific down regulation may provide an active and precise method for constraining an excessive immune response and avoiding bypass suppression of necessary immune responses to other antigens.
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, Shandong 271000, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Institute of Immunology, Taishan Medical University, Taian, Shandong 271000, China.
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Zhenglong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007114:Immunization; D056747:Immunomodulation; D016130:Immunophenotyping; D018655:Lymphocyte Count; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D011948:Receptors, Antigen, T-Cell