The roles of intrahepatic V alpha 14(+) 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 Salm onella infection, we examined serum alanine transaminase (ALT), histopathol ogy, and bacterial numbers in liver after infection with Salmonella cholera esuis strain 31N-1 in mice genetically lacking TCR alpha beta(+), CD4(+), C D8(+), or NK1.1(+)T cells with C57BL/6 background. In control (+/+) mice, s erum 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, liv er injury, as assessed by serum ALT level and histological examination, was significantly suppressed on day 7 after Salmonella infection but the numbe rs of bacteria in liver did not differ from those in normal mice, suggestin g that alpha beta T cells are responsible for liver injury induced by Salmo nella infection. To further determine which subsets in alpha beta T cells a re important for the liver injury, we compared serum ALT level in mice gene tically lacking CD4, CD8, beta 2-microglobulin (beta 2m, IA beta, or J alph a 281 after Salmonella infection. In CD4(-/-) mice, serum ALT was significa ntly lower in comparison with control mice, but there was no difference in serum ALT levels in CD8(-/-) and IA beta(-/-) mice from that in control mic e. Notably, serum ALT levels and pathological lesions in liver were signifi cantly decreased in beta 2m(-/-) or J alpha 281(-/-)-mice, which lacked in NK1.1(+) T cells bearing TCR V alpha 14-J alpha 281 specific for beta 2m-as sociated CD1d, following Salmonella infection. Taken together, it is sugges ted that alpha beta T cells bearing NK1.1 and CD4 may be main effector cell s for liver injury after Salmonella infection.