title: Thymic function is maintained during Salmonella-induced atrophy and recovery.
abstract: Thymic atrophy is a frequent consequence of infection with bacteria, viruses, and parasites and is considered a common virulence trait between pathogens. Multiple reasons have been proposed to explain this atrophy, including premature egress of immature thymocytes, increased apoptosis, or thymic shutdown to prevent tolerance to the pathogen from developing. The severe loss in thymic cell number can reflect an equally dramatic reduction in thymic output, potentially reducing peripheral T cell numbers. In this study, we examine the relationship between systemic Salmonella infection and thymic function. During infection, naive T cell numbers in peripheral lymphoid organs increase. Nevertheless, this occurs despite a pronounced thymic atrophy caused by viable bacteria, with a peak 50-fold reduction in thymocyte numbers. Thymic atrophy is not dependent upon homeostatic feedback from peripheral T cells or on regulation of endogenous glucocorticoids, as demonstrated by infection of genetically altered mice. Once bacterial numbers fall, thymocyte numbers recover, and this is associated with increases in the proportion and proliferation of early thymic progenitors. During atrophy, thymic T cell maturation is maintained, and single-joint TCR rearrangement excision circle analysis reveals there is only a modest fall in recent CD4(+) thymic emigrants in secondary lymphoid tissues. Thus, thymic atrophy does not necessarily result in a matching dysfunctional T cell output, and thymic homeostasis can constantly adjust to systemic infection to ensure that naive T cell output is maintained.
authors.affiliation: Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, Institute for Biomedical Research, Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Ewan A
authors.initials: EA
authors.lastname: Ross
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Coughlan
authors.forename: Adriana
authors.initials: A
authors.lastname: Flores-Langarica
authors.forename: Sian
authors.initials: S
authors.lastname: Lax
authors.forename: Julia
authors.initials: J
authors.lastname: Nicholson
authors.forename: Guillaume E
authors.initials: GE
authors.lastname: Desanti
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Marshall
authors.forename: Saeeda
authors.initials: S
authors.lastname: Bobat
authors.forename: Jessica
authors.initials: J
authors.lastname: Hitchcock
authors.forename: Andrea
authors.initials: A
authors.lastname: White
authors.forename: William E
authors.initials: WE
authors.lastname: Jenkinson
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
authors.forename: Gareth G
authors.initials: GG
authors.lastname: Lavery
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D001284:Atrophy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D051379:Mice; D020127:Recovery of Function / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012486:Salmonella typhimurium / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*