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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Jehl SP,Doling AM,Giddings KS,Phalipon A,Sansonetti PJ,Goldberg MB,Starnbach MN

doi

10.1128/IAI.00939-10

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

2021-30

issue

5

eissn

0019-9567

issn

1098-5522

pii

IAI.00939-10

journal_volume

79

pub_type

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