Projects per year
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 language | English |
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Pages (from-to) | 4266-4274 |
Number of pages | 9 |
Journal | Journal of Immunology |
Volume | 189 |
Issue number | 9 |
Early online date | 19 Sept 2012 |
DOIs | |
Publication status | Published - 1 Nov 2012 |
Keywords
- Cell Movement
- Animals
- Thymus Gland
- Salmonella Infections
- Recovery of Function
- Cell Differentiation
- Mice
- Atrophy
- Salmonella typhimurium
- CD4-Positive T-Lymphocytes
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Dive into the research topics of 'Thymic function is maintained during Salmonella-induced atrophy and recovery'. Together they form a unique fingerprint.Projects
- 4 Finished
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Cortical Thymic Epithelium: Defining Developmental Pathways and Specialisation for Positive Selection
3/01/11 → 2/01/14
Project: Research Councils
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Generation of Intrathymic Microenvironments to Establish T-Cell Tolerance
Anderson, G., Jenkinson, E. & Lane, P.
1/10/10 → 30/09/15
Project: Research Councils
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Investigating Hexose-6-Phosphate Dehydrogenase in the Control of Skeletal Muscle Function and Carbohydrate Metabolism
Lavery, G.
Biotechnology & Biological Sciences Research Council
1/09/09 → 31/08/14
Project: Research Councils
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Activities of Salmonella Flagellin: FliCing Immunity On and Off and from Th1 to Th2
Biotechnology & Biological Sciences Research Council
19/12/08 → 18/12/11
Project: Research Councils