The roles of intrahepatic Valpha14(+) NK1.1(+) T cells for liver injury induced by Salmonella infection in mice.

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.