title: Differential modulating effect of natural killer (NK) T cells on interferon-γ production and cytotoxic function of NK cells and its relationship with NK subsets in Chlamydia muridarum infection.
abstract: Natural killer T (NKT) cells are a newly identified T-cell population with potential immunomodulatory functions. Several studies have shown modulating effects of NKT cells activated by α-galactosylceramide, a model antigen, on NK cell function. We here report a differential modulating effect of NKT cells on the interferon-γ (IFN-γ) production and cytolytic function of NK cells in a chlamydial infection model, using NKT-cell-deficient mice and antibody blocking (anti-CD1d monoclonal antibody) approaches. Our results showed that both NKT and NK cells became activated and produced IFN-γ following Chlamydia muridarum infection in vitro and in vivo. The NK cells in NKT-cell-deficient mice and CD1d-blocked mice showed decreased CD69 expression, cellular expansion and IFN-γ production but surprisingly showed increased cytolytic activity (degranulation) of immature and more mature NK cell subsets, suggesting an inhibitory role of NKT cells on NK cell killing activity. The results suggest that NKT cells preferentially promote IFN-γ production but are inhibitory for the cytotoxic function of NK cells in this infection model. Furthermore, the differential modulating effect of NKT cells on the IFN-γ production and cytotoxicity of NK cells was observed in immature and mature NK cell subsets, although it was more dramatic in the relatively mature CD11b(high)  CD27(high) NK cell subset. This finding demonstrates the complexity of innate cell interactions in infection and the possible differential impact of NKT cells on the variable functional aspects of other cell(s) even in one infection setting.
authors: Department of Medical Microbiology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Lei
authors: L
authors: Zhao
authors: Xiaoling
authors: X
authors: Gao
authors: Ying
authors: Y
authors: Peng
authors: Antony G
authors: AG
authors: Joyee
authors: Hong
authors: H
authors: Bai
authors: Shuhe
authors: S
authors: Wang
authors: Jie
authors: J
authors: Yang
authors: Weiming
authors: W
authors: Zhao
authors: Xi
authors: X
authors: Yang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D055610:Antigens, CD1d / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D018845:CD11 Antigens / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D007371:Interferon-gamma; D037181:Lectins, C-Type; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000099192:CD69 Antigens