title: The roles of intrahepatic Valpha14(+) NK1.1(+) T cells for liver injury induced by Salmonella infection in mice.
abstract: To investigate the roles of intrahepatic T cells in liver injury after Salmonella infection, we examined serum alanine transaminase (ALT), histopathology, and bacterial numbers in liver after infection with Salmonella choleraesuis strain 31N-1 in mice genetically lacking TCRalpha beta+, CD4(+), CD8(+), or NK1.1(+)T cells with C57BL/6 background. In control (+/+) mice, serum ALT reached a peak level by day 7 after an intraperitoneal inoculation of 2 x 10(6) CFU Salmonella choleraesuis 31N-1. In TCR-beta-/- mice, liver injury, as assessed by serum ALT level and histological examination, was significantly suppressed on day 7 after Salmonella infection but the numbers of bacteria in liver did not differ from those in normal mice, suggesting that alpha beta T cells are responsible for liver injury induced by Salmonella infection. To further determine which subsets in alpha beta T cells are important for the liver injury, we compared serum ALT level in mice genetically lacking CD4, CD8, beta2-microglobulin (beta2m, IAbeta, or Jalpha281 after Salmonella infection. In CD4(-/-) mice, serum ALT was significantly lower in comparison with control mice, but there was no difference in serum ALT levels in CD8(-/-) and IAbeta-/- mice from that in control mice. Notably, serum ALT levels and pathological lesions in liver were significantly decreased in beta2m-/- or Jalpha281(-/-) mice, which lacked in NK1.1(+) T cells bearing TCR Valpha14-Jalpha281 specific for beta2m-associated CD1d, following Salmonella infection. Taken together, it is suggested that alpha beta T cells bearing NK1.1 and CD4 may be main effector cells for liver injury after Salmonella infection.
authors.affiliation: Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishigami
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: Y
authors.initials: Y
authors.lastname: Naiki
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.forename: T
authors.initials: T
authors.lastname: Kawano
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: S
authors.initials: S
authors.lastname: Kakumu
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology; D016827:CD8 Antigens / Q000235:genetics / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D019674:Genes, T-Cell Receptor beta; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012475:Salmonella / Q000254:growth & development*; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D007371:Interferon-gamma; D000410:Alanine Transaminase