The frequency of double-positive thymocytes expressing an αβ TCR clonotype regulates peripheral CD4 T cell compartment homeostasis

Amy J. Reed, Yasaman Zarrabi, Alison L. Perate, Arjun Jeganathan, Ali Naji, Hooman Noorchashm

Research output: Contribution to journalArticle

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Abstract

The present study aimed to determine whether the frequency of double positive (DP) thymocytes expressing αβ T-cell receptor (TCR) clonotypes at the time of selection regulates peripheral CD4 T-cell compartment size. Scid recipients were inoculated with various ratios of TCR Cα0/0 and wild-type bone marrow (BM) stem cells. Increasing the frequency of TCR Cα0/0 thymocytes at steady-state introduced a graded decrease in the maturation probability of the total DP thymocyte pool. At 12-14 weeks following BM inoculation, the frequency of TCR Cα0/0 DP thymocytes was inversely correlated with that of CD4 single positive (SP) thymocytes. Notwithstanding, a decreased frequency of wild-type DP thymocytes led to a marked increase in their transit efficiency from the DP to SP compartments. The frequency-dependent increase in thymocyte transit efficiency was associated with a CD4 SP cell surface phenotype indicative of increased antigenic experience. Importantly, the frequency of DP thymocytes capable of expressing TCR clonotypes dictated the steady-state size of the peripheral CD4 T cell compartment and its potential for homeostatic proliferation. Collectively, these results indicate that the efficiency of DP to CD4 SP transit is a frequency dependent process, which determines (1) the steady-state size of the peripheral T cell compartment and (2) the threshold for homeostatic expansion of peripheral CD4 T cells.

Original languageEnglish (US)
Pages (from-to)400-407
Number of pages8
JournalImmunology
Volume116
Issue number3
DOIs
Publication statusPublished - Nov 1 2005

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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