Determination of thymic function direct from peripheral blood: A validated modification to an established method

A. R. Lorenzi, Angela Margaret Patterson, A. Pratt, M. Jefferson, C. E. Chapman, F. Ponchel, J. D. Isaacs

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The thymus contributes naive, self MHC reactive, self tolerant T cells to the peripheral immune system throughout life, albeit with a log-linear decline with age. Quantification of thymic function is clinically relevant in the setting of lymphoablation, but a phenotypic marker distinguishing recent thymic emigrants from long lived naive T cells remains elusive. T cell receptor excision circles (TREC) are present in thymocytes exiting the thymus and quantification of the most frequent of these, the delta rec-Psi J alpha rearrangement has been widely used as a measure of recent thymic function. However, interpretation of results presented as TREC per cell has been criticised on the basis that extra-thymic cellular proliferation impacts on peripherally determined TREC numbers. TREC/ml is now considered to be more representative of thymic function than TREC/cell, especially where significant cellular proliferation occurs (e.g. during reconstitution following stem cell transplantation). Here we describe the validation of a novel variation to the established assay, directly quantifying TREC/ ml from 300 mu l whole blood. We show the assay to be reproducible, robust and stable longitudinally and we show equivalence of performance when compared with more standard assays. This assay particularly lends itself to the measurement of thymic function in children and where monitoring clinical variables is limited by tissue availability. (C) 2008 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)185-194
Number of pages10
JournalJournal of Immunological Methods
Volume339
Issue number2
Early online date12 Oct 2008
DOIs
Publication statusPublished - 31 Dec 2008

Keywords

  • TREC
  • thymic function
  • recent thymic emigrants
  • stem cell transplantation
  • thymic reconstitution
  • paediatric
  • stem-cell transplantation
  • bone-marrow-transplantation
  • receptor excision circles
  • T-cells
  • HIV-infection
  • immune reconstitution
  • output
  • gene
  • age
  • recombination
  • Thymic function
  • Recent thymic emigrants
  • Stem cell transplantation
  • Thymic reconstitution
  • Paediatric

Cite this

Lorenzi, A. R., Patterson, A. M., Pratt, A., Jefferson, M., Chapman, C. E., Ponchel, F., & Isaacs, J. D. (2008). Determination of thymic function direct from peripheral blood: A validated modification to an established method. Journal of Immunological Methods, 339(2), 185-194. https://doi.org/10.1016/j.jim.2008.09.013