title: Protective roles of B and T lymphocyte attenuator in NKT cell-mediated experimental hepatitis.
abstract: Although B and T lymphocyte attenuator (BTLA) was originally identified as an inhibitory coreceptor selectively expressed on Th1 cells and B cells, recent studies have revealed that BTLA is expressed on a variety of cells, including macrophages, dendritic cells, and NK cells, and modulates their functions. However, the role of BTLA in the regulation of NKT cell function remains unknown. In this study, we found that BTLA was expressed on NKT cells at the levels similar to those on T cells and that BTLA-deficient (BTLA(-/-)) NKT cells produced larger amounts of IL-4 and IFN-gamma upon alpha-glactosylceramide stimulation as compared with wild-type (WT) NKT cells. In vivo, BTLA(-/-) mice produced larger amounts of IL-4 and IFN-gamma upon Con A injection and were more susceptible to Con A-induced hepatitis than WT mice. In addition, the augmentation of Con A-induced hepatitis in BTLA(-/-) mice was not observed in BTLA/NKT-double deficient mice. Moreover, NKT(-/-) mice reconstituted with BTLA(-/-) NKT cells were significantly more susceptible to Con A-induced hepatitis as compared with NKT (-/-) mice reconstituted with WT NKT cells. These results suggest that BTLA functions as the inhibitory coreceptor of NKT cells and plays a critical role in the prevention of NKT cell-mediated liver injury.
authors: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan.
authors: Arifumi
authors: A
authors: Iwata
authors: Norihiko
authors: N
authors: Watanabe
authors: Yoshihiro
authors: Y
authors: Oya
authors: Takayoshi
authors: T
authors: Owada
authors: Kei
authors: K
authors: Ikeda
authors: Akira
authors: A
authors: Suto
authors: Shin-ichiro
authors: S
authors: Kagami
authors: Koichi
authors: K
authors: Hirose
authors: Hiroko
authors: H
authors: Kanari
authors: Saki
authors: S
authors: Kawashima
authors: Toshinori
authors: T
authors: Nakayama
authors: Masaru
authors: M
authors: Taniguchi
authors: Itsuo
authors: I
authors: Iwamoto
authors: Hiroshi
authors: H
authors: Nakajima
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006505:Hepatitis / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D055611:Natural Killer T-Cells / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism
chemical_list: C488868:BTLA protein, mouse; D008934:Mitogens; D011971:Receptors, Immunologic; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma