Heterogeneity in thymic emigrants: implications for thymectomy and immunosenescence

PLoS One. 2013;8(2):e49554. doi: 10.1371/journal.pone.0049554. Epub 2013 Feb 27.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aging / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Adhesion Molecules / metabolism
  • Child
  • Child, Preschool
  • Emigrants and Immigrants
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Models, Biological
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Thymectomy
  • Thymus Gland / immunology*
  • Young Adult

Substances

  • Cell Adhesion Molecules
  • PTK7 protein, human
  • Receptor Protein-Tyrosine Kinases