Age-dependent incidence, time course, and consequences of thymic renewal in adults.
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.
Hakim
Frances T
FT
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. fhakim@helix.nih.gov
Memon
Sarfraz A
SA
Cepeda
Rosemarie
R
Jones
Elizabeth C
EC
Chow
Catherine K
CK
Kasten-Sportes
Claude
C
Odom
Jeanne
J
Vance
Barbara A
BA
Christensen
Barbara L
BL
Mackall
Crystal L
CL
Gress
Ronald E
RE
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
D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens