title: Propionibacterium acnes treatment diminishes CD4+ NK1.1+ T cells but induces type I T cells in the liver by induction of IL-12 and IL-18 production from Kupffer cells.
abstract: LPS injection into normal mice does not induce liver injury, while the same treatment of Propionibacterium acnes-primed mice induces severe liver injury, indicating that P. acnes treatment renders the mice susceptible to LPS. Since IFN-gamma sensitizes macrophages to LPS, we investigated the mechanism of induction and activation of IFN-gamma-producing (type 1) T cells by P. acnes. Twenty percent of liver lymphocytes of C57BL/6 mice are CD4+ NK1.1+ T cells that promptly produce IL-4 in response to anti-CD3 in vitro. However, P. acnes treatment diminished these lymphocytes. Therefore, liver lymphocytes from P. acnes-primed mice showed reduced IL-4 production. Furthermore, P. acnes treatment induced CD4- type 1 T cells in the liver. Isolated P. acnes-elicited Kupffer cells produced IL-12 and to a lesser degree IL-18 in vitro. Injection of anti-IL-12 Ab totally abrogated these actions of P. acnes, while injection of anti-IL-18 Ab caused only partial abrogation. Thus, administration of P. acnes diminished CD4+ NK1.1+ T cells, but induced type 1 T cells in the liver by induction of IL-12 and IL-18 production. Injection of IL-12 (approximately 1,000 ng) dose dependently diminished CD4+ NK1.1+ T cells, but induced type 1 T cells. In contrast, injection of IL-18 (approximately 1,000 ng) failed, although injection of a much larger dose of IL-18 (10,000 ng) or IL-18 (approximately 1,000 ng) with suboptimal doses of IL-12 (1-100 ng) diminished CD4+ NK1.1+ T cells in a dose-dependent manner. Thus, P. acnes treatment renders the mice highly susceptible to LPS by induction and activation of type 1 T cells.
authors.affiliation: Third Department of Internal Medicine, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsui
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: H
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Y
authors.initials: Y
authors.lastname: Hyodo
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Hiroishi
authors.forename: N
authors.initials: N
authors.lastname: Kawada
authors.forename: H
authors.initials: H
authors.lastname: Okamura
authors.forename: K
authors.initials: K
authors.lastname: Nakanishi
authors.forename: K
authors.initials: K
authors.lastname: Higashino
mesh_terms: D000818:Animals; D015704:CD4 Antigens; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D020382:Interleukin-18; D007694:Killer Cells, Natural / Q000276:immunology*; D007728:Kupffer Cells / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011425:Propionibacterium acnes; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D020382:Interleukin-18; D008070:Lipopolysaccharides; D018664:Interleukin-12