Selective culling of high avidity antigen-specific CD4 + T cells after virulent Salmonella infection

James M. Ertelt, Tanner M. Johanns, Margaret A. Mysz, Minelva R Nanton, Jared H. Rowe, Marijo N. Aguilera, Sing Sing Way

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)487-497
Number of pages11
JournalImmunology
Volume134
Issue number4
DOIs
StatePublished - Dec 2011

Keywords

  • Bacteria/bacterial infection
  • CD4/helper T cells
  • Infection
  • T-cell receptor
  • Tetramers

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