title: Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection.
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.
authors: Department of Pediatrics, University of Minnesota School of Medicine, Center for Microbiology and Infectious Disease Translational Research, Minneapolis, MN 55455, USA.
authors: James M
authors: JM
authors: Ertelt
authors: Tanner M
authors: TM
authors: Johanns
authors: Margaret A
authors: MA
authors: Mysz
authors: Minelva R
authors: MR
authors: Nanton
authors: Jared H
authors: JH
authors: Rowe
authors: Marijo N
authors: MN
authors: Aguilera
authors: Sing Sing
authors: SS
authors: Way
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060085:Coinfection; D005260:Female; D008089:Listeria monocytogenes / Q000235:genetics; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012475:Salmonella; D012481:Salmonella Infections, Animal / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008565:Membrane Proteins; C440638:SPI-2 protein, Salmonella