Role of T cells in a murine model of Escherichia coli sepsis.
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.
van Schaik
Sandrijn M
SM
Department of Pediatrics, University of California San Francisco School of Medicine, San Francisco, CA 94143-0106, USA. vanschaiks@peds.ucsf.edu
Abbas
Abul K
AK
D000818:Animals; D015704:CD4 Antigens; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology*; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D016207:Cytokines; D007371:Interferon-gamma