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Selective culling of high avidity antigen‐specific CD4 + T cells after virulent Salmonella infection
Author(s) -
Ertelt James M.,
Johanns Tanner M.,
Mysz Margaret A.,
Nanton Minelva R.,
Rowe Jared H.,
Aguilera Marijo N.,
Way Sing Sing
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03510.x
Subject(s) - biology , antigen , microbiology and biotechnology , immune system , avidity , population , virulence , salmonella , salmonella infection , t cell , virology , immunology , bacteria , medicine , biochemistry , genetics , environmental health , gene
Summary Typhoid fever is a persistent infection caused by host‐adapted Salmonella strains adept at circumventing immune‐mediated host defences. Given the importance of T cells in protection, the culling of activated CD4 + T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen‐specific CD4 + T cells after virulent Salmonella infection requires SPI‐2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella ‐expressed antigens, but extends to CD4 + T cells primed to expand by co‐infection with recombinant Listeria monocytogenes . Unexpectedly, however, the loss of activated CD4 + T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4 + T cells was not reproduced among the endogenous repertoire of antigen‐specific CD4 + T cells identified with MHC class II tetramer. Analysis of T‐cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4 + T‐cell subsets after Salmonella co‐infection that is associated with the purging of antigen‐specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4 + T‐cell subsets, which re‐shapes the repertoire of antigen‐specific T cells that persist later after infection.