UCSF

To study the role of T cells in gram-negative sepsis, we developed a mouse model in which i.v. injection of Escherichia coli results in severe systemic illness, with high mortality rates after day 5. A large proportion of both CD4(+) and CD8(+) T cells are activated within 1 day after infection, as evidenced by up-regulation of CD69 and down-regulation of CD62L. Even more surprisingly, T cell-deficient mice exhibit markedly decreased disease severity compared to WT mice, indicating a pathogenic role of T cells. Mice lacking IFN-gamma also show diminished disease, and exhibit reduced T cell activation. Therefore, the pathogenic role of T cells may be mediated by IFN-gamma. Both T cell- and IFN-gamma-deficient mice have reduced serum IL-6 levels compared to WT mice, suggesting that T cells may stimulate innate immune responses, resulting in enhancement of disease. These data indicate an important role for T cells in a mouse model of E. coli sepsis, and reveal an unexpected early and pathogenic T cell response to this bacterial infection.