Thymic function is maintained during Salmonella-induced atrophy and recovery

Ewan A. Ross, Ruth E. Coughlan, Adriana Flores-Langarica, Sian Lax, Julia Nicholson, Guillaume E. Desanti, Jennifer L. Marshall, Saeeda Bobat, Jessica Hitchcock, Andrea White, William E. Jenkinson, Mahmood Khan, Ian R. Henderson, Gareth G. Lavery, Christopher D. Buckley, Graham Anderson, Adam F. Cunningham*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4266-4274
Number of pages9
JournalJournal of Immunology
Volume189
Issue number9
DOIs
Publication statusPublished - 1 Nov 2012

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Ross, E. A., Coughlan, R. E., Flores-Langarica, A., Lax, S., Nicholson, J., Desanti, G. E., Marshall, J. L., Bobat, S., Hitchcock, J., White, A., Jenkinson, W. E., Khan, M., Henderson, I. R., Lavery, G. G., Buckley, C. D., Anderson, G., & Cunningham, A. F. (2012). Thymic function is maintained during Salmonella-induced atrophy and recovery. Journal of Immunology, 189(9), 4266-4274. https://doi.org/10.4049/jimmunol.1200070