Yates, A. J. , Bains, I. and Callard, R. E. (2013) Heterogeneity in thymic emigrants: implications for thymectomy and immunosenescence. PLoS ONE, 8(2), e49554. (doi: 10.1371/journal.pone.0049554) (PMID:23468830) (PMCID:PMC3584139)
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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0049554
Abstract
The development of mature, antigen-inexperienced (naive) T cells begins in the thymus and continues after export into the periphery. Post-thymic maturation of naive T cells, in humans, coincides with the progressive loss of markers such as protein tyrosine kinase 7 (PTK7) and platelet endothelial cell adhesion molecule-1 (CD31). As a consequence, subpopulations of naive T cells can be recognised raising questions about the processes that give rise to the loss of these markers and their exact relationship to recent thymic emigrants (RTE). Here, we combine a mathematical survival analysis approach and data from healthy and thymectomised humans to understand the apparent persistence of populations of ‘veteran’ PTK7+T cells in thymectomised individuals. We show that a model of heterogeneity in rates of maturation, possibly linked to natural variation in TCR signalling thresholds or affinity for self-antigens, can explain the data. This model of maturation predicts that the average post-thymic age of PTK7+T cells will increase linearly with the age of the host suggesting that, despite the immature phenotype, PTK7+cells do not necessarily represent a population of RTE. Further, the model predicts an accelerated increase in the average post-thymic age of residual PTK7+T cells following thymectomy and may also explain in part the prematurely aged phenotype of the naive T cell pool in individuals thymectomised early in life.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Yates, Professor Andrew |
| Authors: | Yates, A. J., Bains, I., and Callard, R. E. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | PLoS ONE |
| Publisher: | Public Library of Science |
| ISSN: | 1932-6203 |
| ISSN (Online): | 1932-6203 |
| Copyright Holders: | Copyright © 2013 The Authors |
| First Published: | First published in PLoS One 8(2):e49554 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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