title: Age-dependent incidence, time course, and consequences of thymic renewal in adults.
abstract: Homeostatic regulation of T cells involves an ongoing balance of new T cell generation, peripheral expansion, and turnover. The recovery of T cells when this balance is disrupted provides insight into the mechanisms that govern homeostasis. In a long-term, single cohort study, we assessed the role of thymic function after autologous transplant in adults, correlating serial computed tomography imaging of thymic size with concurrent measurements of peripheral CD4(+) T cell populations. We established the age-dependent incidence, time course, and duration of thymic enlargement in adults and demonstrated that these changes were correlated with peripheral recovery of naive CD45RA(+)CD62L(+) and signal-joint TCR rearrangement excision circle-bearing CD4(+) populations with broad TCR diversity. Furthermore, we demonstrated that renewed thymopoiesis was critical for the restoration of peripheral CD4(+) T cell populations. This recovery encompassed the recovery of normal CD4(+) T cell numbers, a low ratio of effector to central memory cells, and a broad repertoire of TCR Vbeta diversity among these memory cells. These data define the timeline and consequences of renewal of adult thymopoietic activity at levels able to quantitatively restore peripheral T cell populations. They further suggest that structural thymic regrowth serves as a basis for the regeneration of peripheral T cell populations.
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. fhakim@helix.nih.gov
authors.forename: Frances T
authors.initials: FT
authors.lastname: Hakim
authors.forename: Sarfraz A
authors.initials: SA
authors.lastname: Memon
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Cepeda
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Jones
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Chow
authors.forename: Claude
authors.initials: C
authors.lastname: Kasten-Sportes
authors.forename: Jeanne
authors.initials: J
authors.lastname: Odom
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Vance
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Christensen
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Mackall
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D006706:Homeostasis; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013223:Statistics as Topic; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology* / Q000637:transplantation; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens