title: Heterogeneity in thymic emigrants: implications for thymectomy and immunosenescence.
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.
authors.affiliation: Immune Cell Biology, National Institute for Medical Research, Mill Hill, London, United Kingdom. bains@nimr.mrc.ac.uk
authors.forename: Iren
authors.initials: I
authors.lastname: Bains
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Yates
authors.forename: Robin E
authors.initials: RE
authors.lastname: Callard
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D054242:Emigrants and Immigrants; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D008954:Models, Biological; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases