Sublethal total body irradiation causes long-term deficits in thymus function by reducing lymphoid progenitors Journal Article

   

Authors:	Xiao, S.; Shterev, I. D.; Zhang, W.; Young, L.; Shieh, J. H.; Moore, M.; van den Brink, M.; Sempowski, G. D.; Manley, N. R.
Article Title:	Sublethal total body irradiation causes long-term deficits in thymus function by reducing lymphoid progenitors
Abstract:	Total body irradiation (TBI) damages hematopoietic cells in the bone marrow and thymus; however, the long-term effects of irradiation with aging remain unclear. In this study, we found that the impact of radiation on thymopoiesis in mice varied by sex and dose but, overall, thymopoiesis remained suppressed for ?12 mo after a single exposure. Male and female mice showed a long-term dose-dependent reduction in thymic cKit+ lymphoid progenitors that was maintained throughout life. Damage to hematopoietic stem cells (HSCs) in the bone marrow was dose dependent, with as little as 0.5 Gy causing a significant long-term reduction. In addition, the potential for T lineage commitment was radiation sensitive with aging. Overall, the impact of irradiation on the hematopoietic lineage was more severe in females. In contrast, the rate of decline in thymic epithelial cell numbers with age was radiation-sensitive only in males, and other characteristics including Ccl25 transcription were unaffected. Taken together, these data suggest that long-term suppression of thymopoiesis after sublethal irradiation was primarily due to fewer progenitors in the BM combined with reduced potential for T lineage commitment. A single irradiation dose also caused synchronization of thymopoiesis, with a periodic thymocyte differentiation profile persisting for at least 12 mo postirradiation. This study suggests that the number and capability of HSCs for T cell production can be dramatically and permanently damaged after a single relatively low TBI dose, accelerating aging-associated thymic involution. Our findings may impact evaluation and therapeutic intervention of human TBI events. Copyright © 2017 by The American Association of Immunologists, Inc.
Journal Title:	Journal of Immunology
Volume:	199
Issue:	8
ISSN:	0022-1767
Publisher:	The American Association of Immunologists, Inc
Date Published:	2017-10-15
Start Page:	2701
End Page:	2712
Language:	English
DOI:	10.4049/jimmunol.1600934
PROVIDER:	scopus
PMCID:	PMC5659725
PUBMED:	28931604
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85031493134&doi=10.4049%2fjimmunol.1600934&partnerID=40&md5=1094bc3aacd760caf07c49934ae2df71
Notes:	Article -- Export Date: 2 November 2017 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/116591