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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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02874973
Contributor : Armelle Phalipon <>
Submitted on : Friday, June 19, 2020 - 12:21:46 PM
Last modification on : Wednesday, October 14, 2020 - 3:48:22 AM

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Stephanie Jehl, Amy Doling, Kara Giddings, Armelle Phalipon, Philippe Sansonetti, et al.. Antigen-Specific CD8 + T Cells Fail To Respond to Shigella flexneri. Infection and Immunity, American Society for Microbiology, 2011, 79 (5), pp.2021-2030. ⟨10.1128/IAI.00939-10⟩. ⟨pasteur-02874973⟩

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