Fatal recall responses mediated by CD8 T cells during intracellular bacterial challenge infection.
The roles(s) of CD8 T cells during infections by intracellular bacteria that reside in host cell endocytic compartments are not well understood. Our previous studies in a mouse model of human monocytotropic ehrlichiosis indicated that CD8 T cells are not essential for immunity. However, we have observed an unexpected role for these cells during challenge infection. Although immunocompetent mice cleared a primary low-dose (nonfatal) Ixodes ovatus ehrlichia infection, a secondary low-dose challenge infection resulted in fatal disease and loss of control of infection. The outcome was CD8-dependent, because CD8-deficient mice survived secondary low-dose challenge infection. Moreover, effector and/or memory phenotype CD8 T cells were responsible, because adoptive transfer of purified CD44(high) CD8 T cells to naive mice induced fatal responses following a primary low-dose infection. The fatal responses were perforin- and Fas ligand-independent, and were associated with high serum concentrations of TNF-alpha and CCL2, and low levels of IL-10. Accordingly, blockade of either TNF-alpha or CCL2 ameliorated fatal recall responses, and in vitro coculture of memory CD8 T cells and Ixodes ovatus ehrlichia-infected peritoneal exudate cells resulted in substantial increases in TNF-alpha and CCL2. Thus, during monocytotropic ehrlichiosis, inflammatory cytokine production, by CD8 T cells and/or other host cells, can trigger chemokine-dependent disease. These findings highlight a novel role for CD8 T cells, and reveal that live vaccines for intracellular bacteria can, under some conditions, induce undesirable consequences.
Bitsaktsis
Constantine
C
Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12201, USA.
Winslow
Gary
G
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004536:Ehrlichia / Q000276:immunology; D016873:Ehrlichiosis / Q000276:immunology* / Q000503:physiopathology; D005434:Flow Cytometry; D007156:Immunologic Memory; D018884:Ixodes; D051379:Mice; D018345:Mice, Knockout
D016207:Cytokines