title: Antigen-specific CD8(+) T cells fail to respond to Shigella flexneri.
abstract: CD8(+) T lymphocytes often play a primary role in adaptive immunity to cytosolic microbial pathogens. Surprisingly, CD8(+) T cells are not required for protective immunity to the enteric pathogen Shigella flexneri, despite the ability of Shigella to actively secrete proteins into the host cytoplasm, a location from which antigenic peptides are processed for presentation to CD8(+) T cells. To determine why CD8(+) T cells fail to play a role in adaptive immunity to S. flexneri, we investigated whether antigen-specific CD8(+) T cells are primed during infection but are unable to confer protection or, alternatively, whether T cells fail to be primed. To test whether Shigella is capable of stimulating an antigen-specific CD8(+) T-cell response, we created an S. flexneri strain that constitutively secretes a viral CD8(+) T-cell epitope via the Shigella type III secretion system and characterized the CD8(+) T-cell response to this strain both in mice and in cultured cells. Surprisingly, no T cells specific for the viral epitope were stimulated in mice infected with this strain, and cells infected with the recombinant strain were not targeted by epitope-specific T cells. Additionally, we found that the usually robust T-cell response to antigens artificially introduced into the cytoplasm of cultured cells was significantly reduced when the antigen-presenting cell was infected with Shigella. Collectively, these results suggest that antigen-specific CD8(+) T cells are not primed during S. flexneri infection and, as a result, afford little protection to the host during primary or subsequent infection.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Jehl
authors.forename: Amy M
authors.initials: AM
authors.lastname: Doling
authors.forename: Kara S
authors.initials: KS
authors.lastname: Giddings
authors.forename: Armelle
authors.initials: A
authors.lastname: Phalipon
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: Marcia B
authors.initials: MB
authors.lastname: Goldberg
authors.forename: Michael N
authors.initials: MN
authors.lastname: Starnbach
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004405:Dysentery, Bacillary / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012763:Shigella flexneri / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte