title: Low-dose Salmonella infection evades activation of flagellin-specific CD4 T cells.
abstract: Many pathogens can establish a lethal infection from relatively small inocula, yet the effect of infectious dose upon CD4 T cell activation is not clearly understood. This issue was examined by tracking Salmonella flagellin-specific SM1 T cells in vivo, after i.v. and oral challenge of mice with virulent Salmonella typhimurium. SM1 T cells rapidly expressed activation markers and expanded in response to high-dose infection but remained completely unresponsive in mice challenged with low doses of Salmonella. SM1 T cells, in these mice, remained unresponsive, despite massive bacterial replication in vivo. Naive SM1 T cells in low-dose Salmonella-infected mice were activated rapidly after the injection of flagellin peptide, demonstrating that these T cells were fully capable of responding, ruling out the possibility of a bacterial-induced suppressive environment. The inability of flagellin-specific SM1 T cells to respond to low-dose infection was not due to Ag down-regulation, because flagellin expression was detected using a functional assay. Together, these data suggest that low-dose Salmonella infection can evade flagellin-specific CD4 T cell activation in vivo.
authors.affiliation: Department of Medicine, Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Joseph
authors.initials: J
authors.lastname: Foley
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ravindran
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McSorley
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D005408:Flagellin / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology / Q000637:transplantation
chemical_list: D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D005408:Flagellin