Late Effects of Exposure to Ionizing Radiation and Age on Human Thymus Morphology and Function.
The thymus is essential for proper development and maintenance of a T-cell repertoire that can respond to newly encountered antigens, but its function can be adversely affected by internal factors such as pregnancy and normal aging or by external stimuli such as stress, infection, chemotherapy and ionizing radiation. We have utilized a unique archive of thymus tissues, obtained from 165 individuals, exposed to the 1945 atomic bomb blast in Hiroshima, to study the long-term effects of receiving up to ∼3 Gy dose of ionizing radiation on human thymus function. A detailed morphometric analysis of thymus activity and architecture in these subjects at the time of their natural deaths was performed using bright-field immunohistochemistry and dual-color immunofluorescence and compared to a separate cohort of nonexposed control subjects. After adjusting for age-related effects, increased hallmarks of thymic involution were observed histologically in individuals exposed to either low (5-200 mGy) or moderate-to-high (>200 mGy) doses of ionizing radiation compared to unirradiated individuals (<5 mGy). Sex-related differences were seen when the analysis was restricted to individuals under 60 years of attained age at sample collection, but were not observed when comparing across the entire age range. This indicates that while females undergo slower involution than males, they ultimately attain similar phenotypes. These findings suggest that even low-dose-radiation exposure can accelerate thymic aging, with decreased thymopoiesis relative to nonexposed controls evident years after exposure. These data were used to develop a model that can predict thymic function during normal aging or in individuals therapeutically or accidentally exposed to radiation.
a   Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Reiko
R
Ito
b   Department of Pathology and the Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina.
Laura P
LP
Hale
c   Department of Pediatrics, Health Informatics Institute, University of South Florida, Tampa, Florida.
Susan M
SM
Geyer
d   Department of Genetics, Paul D. Coverdell Center, University of Georgia, Athens, Georgia.
Jie
J
Li
e   Department of Mathematics, University of California, Davis, California.|f   Department of Mathematics and College of Engineering, University of Georgia, Athens, Georgia.
Andrew
A
Sornborger
a   Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Junko
J
Kajimura
a   Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Yoichiro
Y
Kusunoki
a   Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Kengo
K
Yoshida
g   Departments of Medicine and Immunology, Memorial Sloan Kettering Cancer Center, New York, New York.
Marcel R M
MRM
van den Brink
g   Departments of Medicine and Immunology, Memorial Sloan Kettering Cancer Center, New York, New York.
Seishi
S
Kyoizumi
d   Department of Genetics, Paul D. Coverdell Center, University of Georgia, Athens, Georgia.
Nancy R
NR
Manley
a   Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Kei
K
Nakachi
b   Department of Pathology and the Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina.
Gregory D
GD
Sempowski
D017677:Age Distribution; D000375:Aging / Q000473:pathology*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008137:Longitudinal Studies; D008206:Lymphatic Diseases / Q000401:mortality* / Q000473:pathology* / Q000503:physiopathology; D011829:Radiation Dosage; D000069079:Radiation Exposure / Q000706:statistics & numerical data*; D011832:Radiation Injuries / Q000401:mortality* / Q000473:pathology* / Q000503:physiopathology; D011839:Radiation, Ionizing; D012307:Risk Factors; D017678:Sex Distribution; D015996:Survival Rate; D017741:Survivors / Q000706:statistics & numerical data; D013950:Thymus Gland / Q000473:pathology* / Q000503:physiopathology / Q000528:radiation effects