title: The frequency of double-positive thymocytes expressing an alphabeta TCR clonotype regulates peripheral CD4 T cell compartment homeostasis.
abstract: The present study aimed to determine whether the frequency of double positive (DP) thymocytes expressing alphabeta 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 Calpha(0/0) and wild-type bone marrow (BM) stem cells. Increasing the frequency of TCR Calpha(0/0) 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 Calpha(0/0) 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.
authors.affiliation: Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Reed
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Zarrabi
authors.forename: Alison L
authors.initials: AL
authors.lastname: Perate
authors.forename: Arjun
authors.initials: A
authors.lastname: Jeganathan
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: Hooman
authors.initials: H
authors.lastname: Noorchashm
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta