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

• Published in: Immunology 2005-11, Vol.116 (3), p.400-407
• Main Authors: Reed, Amy J., Zarrabi, Yasaman, Perate, Alison L., Jeganathan, Arjun, Naji, Ali, Noorchashm, Hooman
• Format: Article
• Language: English
• Subjects: cellular differentiation; Original; repertoire development; T lymphocytes; thymus
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2005.02240.x

Summary 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.