The Experts below are selected from a list of 12888 Experts worldwide ranked by ideXlab platform
Laura P. Hale - One of the best experts on this subject based on the ideXlab platform.
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Thymus Function ~ 5 years post-irradiation.
2019Co-Authors: Laura P. Hale, Gowrisankar Rajam, George M. Carlone, Chen Jiang, Kouros Owzar, Greg Dugan, David Caudell, Nelson Chao, Mark J. Cline, Thomas C. RegisterAbstract:sjTREC levels in isolated CD3+ mononuclear cells from peripheral blood are plotted as a Function of age (A) and radiation dose (B). Each point represents a different subject (n = 43). In panel A, the open triangles show values for control, non-irradiated animals and the solid black circles show values for irradiated animals. sjTRECs were associated with age (p = 0.002), but did not vary according to radiation dose. Raw data are provided in S1 Table.
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Late effects of total body irradiation on hematopoietic recovery and immune Function in rhesus macaques
2019Co-Authors: Laura P. Hale, Gowrisankar Rajam, George M. Carlone, Chen Jiang, Kouros Owzar, Greg Dugan, David Caudell, Nelson Chao, Mark J. Cline, Thomas C. RegisterAbstract:While exposure to radiation can be lifesaving in certain settings, it can also potentially result in long-lasting adverse effects, particularly to hematopoietic and immune cells. This study investigated hematopoietic recovery and immune Function in rhesus macaques Cross-sectionally (at a single time point) 2 to 5 years after exposure to a single large dose (6.5 to 8.4 Gray) of total body radiation (TBI) derived from linear accelerator-derived photons (2 MeV, 80 cGy/minute) or Cobalt 60-derived gamma irradiation (60 cGy/min). Hematopoietic recovery was assessed through measurement of complete blood counts, lymphocyte subpopulation analysis, and Thymus Function assessment. Capacity to mount specific antibody responses against rabies, Streptococcus pneumoniae, and tetanus antigens was determined 2 years after TBI. Irradiated macaques showed increased white blood cells, decreased platelets, and decreased frequencies of peripheral blood T cells. Effects of prior radiation on production and export of new T cells by the Thymus was dependent on age at the time of analysis, with evidence of interaction with radiation dose for CD8+ T cells. Irradiated and control animals mounted similar mean antibody responses to proteins from tetanus and rabies and to 10 of 11 serotype-specific pneumococcal polysaccharides. However, irradiated animals uniformly failed to make antibodies against polysaccharides from serotype 5 pneumococci, in contrast to the robust responses of non-irradiated controls. Trends toward decreased serum levels of anti-tetanus IgM and slower peak antibody responses to rabies were also observed. Taken together, these data show that dose-related changes in peripheral blood cells and immune responses to both novel and recall antigens can be detected 2 to 5 years after exposure to whole body radiation. Longer term follow-up data on this cohort and independent validation will be helpful to determine whether these changes persist or whether additional changes become evident with increasing time since radiation, particularly as animals begin to develop aging-related changes in immune Function.
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late effects of exposure to ionizing radiation and age on human Thymus morphology and Function
Radiation Research, 2017Co-Authors: Reiko Ito, Yoichiro Kusunoki, Laura P. Hale, Marcel R M Van Den Brink, Susan Geyer, Andrew T Sornborger, Junko Kajimura, Kengo Yoshida, Seishi KyoizumiAbstract: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.
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naive t cells are maintained in the periphery during the first 3 months of acute hiv 1 infection implications for analysis of Thymus Function
Journal of Clinical Immunology, 2005Co-Authors: Gregory D Sempowski, Laura P. Hale, Charles B Hicks, Joseph J Eron, John Bartlett, Guido Ferrari, Lloyd J Edwards, Susan A Fiscus, Barton F HaynesAbstract:A key determinant of T cell dynamics in HIV-1 infection is the status of thymic Function. To date, most studies of the impact of HIV-1 on the Thymus during early HIV-1 infection have been done in samples collected in the interval of 3-12 months after infection. In this study, we have probed the status of thymic Function and peripheral naive T cells in patients with acute HIV-1 infection diagnosed 18-72 days after the onset of symptoms. We found that peripheral CD4 and CD8 T cell proliferation was initially elevated, then waned over time. The fall in T cell proliferation correlated with a reduction in HIV-1 viral RNA levels and a rise in peripheral blood CD4+ CD25+ T cells. In spite of elevated T cell proliferation early on in primary HIV-1 infection, levels of naive phenotype CD4 and CD8 T cells and T cell receptor excision circle positive cells (sjTREC(+)) remained constant. Taken together with the observation that T cell proliferation normally dilutes peripheral T cell episomal sjTREC levels, these data suggested that thymopoiesis contributes to maintenance of the naive T cell pool during the earliest stages of HIV-1 infection (18-72 days).
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Thymus transplantation in complete digeorge syndrome immunologic and safety evaluations in 12 patients
Blood, 2003Co-Authors: Louise M Markert, Francoise Le Deist, Laura P. Hale, Marcella Sarzotti, Daniel A Ozaki, Gregory D Sempowski, Maria E Rhein, Marilyn J Alexieff, Elizabeth R Hauser, Barton F HaynesAbstract:Complete DiGeorge syndrome is a fatal condition in which infants have no detectable Thymus Function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of Thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured Thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell Function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.
Gregory D Sempowski - One of the best experts on this subject based on the ideXlab platform.
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sublethal total body irradiation causes long term deficits in Thymus Function by reducing lymphoid progenitors
Journal of Immunology, 2017Co-Authors: Shiyun Xiao, Gregory D Sempowski, Ivo D Shterev, Wen Zhang, Lauren Young, Jaehung Shieh, Malcolm A S Moore, Marcel R M Van Den Brink, Nancy R ManleyAbstract: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.
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naive t cells are maintained in the periphery during the first 3 months of acute hiv 1 infection implications for analysis of Thymus Function
Journal of Clinical Immunology, 2005Co-Authors: Gregory D Sempowski, Laura P. Hale, Charles B Hicks, Joseph J Eron, John Bartlett, Guido Ferrari, Lloyd J Edwards, Susan A Fiscus, Barton F HaynesAbstract:A key determinant of T cell dynamics in HIV-1 infection is the status of thymic Function. To date, most studies of the impact of HIV-1 on the Thymus during early HIV-1 infection have been done in samples collected in the interval of 3-12 months after infection. In this study, we have probed the status of thymic Function and peripheral naive T cells in patients with acute HIV-1 infection diagnosed 18-72 days after the onset of symptoms. We found that peripheral CD4 and CD8 T cell proliferation was initially elevated, then waned over time. The fall in T cell proliferation correlated with a reduction in HIV-1 viral RNA levels and a rise in peripheral blood CD4+ CD25+ T cells. In spite of elevated T cell proliferation early on in primary HIV-1 infection, levels of naive phenotype CD4 and CD8 T cells and T cell receptor excision circle positive cells (sjTREC(+)) remained constant. Taken together with the observation that T cell proliferation normally dilutes peripheral T cell episomal sjTREC levels, these data suggested that thymopoiesis contributes to maintenance of the naive T cell pool during the earliest stages of HIV-1 infection (18-72 days).
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Thymus transplantation in complete digeorge syndrome immunologic and safety evaluations in 12 patients
Blood, 2003Co-Authors: Louise M Markert, Francoise Le Deist, Laura P. Hale, Marcella Sarzotti, Daniel A Ozaki, Gregory D Sempowski, Maria E Rhein, Marilyn J Alexieff, Elizabeth R Hauser, Barton F HaynesAbstract:Complete DiGeorge syndrome is a fatal condition in which infants have no detectable Thymus Function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of Thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured Thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell Function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.
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the role of the Thymus in immune reconstitution in aging bone marrow transplantation and hiv 1 infection
Annual Review of Immunology, 2000Co-Authors: Barton F Haynes, Gregory D Sempowski, M L Markert, Dhavalkumar D Patel, Laura P. HaleAbstract:The human Thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that Functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic Function in vivo in adults have provided new opportunities to understand the role that the human Thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the Thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal Thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal Thymus Function that, taken together, support the notion that the human Thymus is Functional well into the sixth decade and plays a role throughout life to optimize human immune system Function.
Barton F Haynes - One of the best experts on this subject based on the ideXlab platform.
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naive t cells are maintained in the periphery during the first 3 months of acute hiv 1 infection implications for analysis of Thymus Function
Journal of Clinical Immunology, 2005Co-Authors: Gregory D Sempowski, Laura P. Hale, Charles B Hicks, Joseph J Eron, John Bartlett, Guido Ferrari, Lloyd J Edwards, Susan A Fiscus, Barton F HaynesAbstract:A key determinant of T cell dynamics in HIV-1 infection is the status of thymic Function. To date, most studies of the impact of HIV-1 on the Thymus during early HIV-1 infection have been done in samples collected in the interval of 3-12 months after infection. In this study, we have probed the status of thymic Function and peripheral naive T cells in patients with acute HIV-1 infection diagnosed 18-72 days after the onset of symptoms. We found that peripheral CD4 and CD8 T cell proliferation was initially elevated, then waned over time. The fall in T cell proliferation correlated with a reduction in HIV-1 viral RNA levels and a rise in peripheral blood CD4+ CD25+ T cells. In spite of elevated T cell proliferation early on in primary HIV-1 infection, levels of naive phenotype CD4 and CD8 T cells and T cell receptor excision circle positive cells (sjTREC(+)) remained constant. Taken together with the observation that T cell proliferation normally dilutes peripheral T cell episomal sjTREC levels, these data suggested that thymopoiesis contributes to maintenance of the naive T cell pool during the earliest stages of HIV-1 infection (18-72 days).
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Thymus transplantation in complete digeorge syndrome immunologic and safety evaluations in 12 patients
Blood, 2003Co-Authors: Louise M Markert, Francoise Le Deist, Laura P. Hale, Marcella Sarzotti, Daniel A Ozaki, Gregory D Sempowski, Maria E Rhein, Marilyn J Alexieff, Elizabeth R Hauser, Barton F HaynesAbstract:Complete DiGeorge syndrome is a fatal condition in which infants have no detectable Thymus Function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of Thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured Thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell Function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.
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the role of the Thymus in immune reconstitution in aging bone marrow transplantation and hiv 1 infection
Annual Review of Immunology, 2000Co-Authors: Barton F Haynes, Gregory D Sempowski, M L Markert, Dhavalkumar D Patel, Laura P. HaleAbstract:The human Thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that Functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic Function in vivo in adults have provided new opportunities to understand the role that the human Thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the Thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal Thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal Thymus Function that, taken together, support the notion that the human Thymus is Functional well into the sixth decade and plays a role throughout life to optimize human immune system Function.
Mireille Dardenne - One of the best experts on this subject based on the ideXlab platform.
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reduced ability of hypothalamic and pituitary extracts from old mice to stimulate thymulin secretion in vitro
Mechanisms of Ageing and Development, 1995Co-Authors: Rodolfo G Goya, Yolanda E Sosa, Marieclaude Gagnerault, Mireille DardenneAbstract:Abstract There is substantial evidence that growth hormone (GH) is particularly important in the control of the age-related decline of Thymus Function. It was therefore of interest: (a) to assess the overall capacity of tissue extracts from mediobasal hypothalamus (MBH), anterior pituitary (AP) and testis, obtained from young (3 months, Yc), middle-aged (13 months, MAc) and old (18 months, Oc) intact C 57 BL 6 mice to stimulate in vitro the release of thymulin, a Zn-bound immunoregulatory thymic peptide, from pure cultures of mouse thymic epithelial cells (TEC); (b) to perform the same evaluation utilizing MBH, AP and testicular extracts from mice of the same age-range but treated for 45 days with a sc dose of ovine GH (2 μg/g body wt) known to stimulate thymulin secretion in vivo. Pituitary hormones were measured by heterologous rat RIAs, whereas thymulin release was estimated by a rosette assay. Untreated animals showed a significant age-dependent increase in the AP content of follicle stimulating hormone but not in other AP hormones. In both control and treated animals, pituitary GH content decreased significantly with age. MBH extracts from C 57 BL 6 males evidenced thymulin-releasing activity on mouse TEC lines. This activity was maximal in the MBH from young animals and declined with the age of the MBH donors. The thymulin-releasing activity of MBHs from GH-treated mice was higher than that of the control animals and showed a less pronounced decline with age. AP extracts from the same animals showed a higher thymulin-releasing activity than did MBH preparations. This activity showed a progressive age-associated reduction in the APs from untreated mice, whereas in the GH-treated group, an age-related decline was only seen in the old donors. Control testicular extracts had little effect on thymulin release whereas GH treatment induced a definite thymulin-release inhibiting activity in the testicular homogenates of our animals which increased progressively with the age of the testis donors. We conclude that the MBH, AP and testis of the young mouse contain factors able to affect directly the endocrine activity of the thymic epithelium. The amount of these substances declines with age and seems to be modulated by GH.
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in vivo effects of growth hormone on Thymus Function in aging mice
Brain Behavior and Immunity, 1992Co-Authors: Rodolfo G Goya, Marieclaude Gagnerault, Maria Leite De Moraes, Wilson Savino, Mireille DardenneAbstract:Abstract It is well demonstrated that the normal Functioning of the Thymus gland is under neuroendocrine control. Thus, steroid, thyroid, and pituitary hormones can affect distinct structural and/or Functional thymic parameters. Particularly growth hormone (GH) was shown to be capable of restoring some Thymus Functions in old individuals. This prompted us to carry out a multiparametric analysis of the Thymus in young, middleaged, and old mice, subjected to GH treatment lasting 3 or 6 weeks. For that, we treated animals with daily injections of ovine GH (2 μg/g BW). Although the general microarchitecture of the Thymus remained unchanged following in vivo GH treatment, there was a clearcut increase in thymulin production, independent of the age group analyzed. Regarding the lymphoid compartment, we could not find evidence of changes in total thymocyte numbers nor in the subsets phenotypically defined by the expression of CD3, CD4, and CD8 antigens. Nonetheless, in GH-treated middle-aged and old mice, the concanavalin A-dependent proliferative response of thymocytes, as well as IL-6 production were enhanced compared to age-matched controls. These findings support the notion that GH has a pleiotropic effect upon the Thymus, Functionally affecting both microenvironmental and lymphoid compartments of the organ.
Nancy R Manley - One of the best experts on this subject based on the ideXlab platform.
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predicted mirna mrna mediated posttranscriptional control associated with differences in cervical and thoracic Thymus Function
Molecular Immunology, 2018Co-Authors: Amanda Freire Assis, Nancy R Manley, Paula B Donate, Janaina Dernowsek, Geraldo Aleixo Silva PassosAbstract:A secondary cervical Thymus (CT) is present in the neck region in about 50% of human and mice. CT in mice is an independent and Functional organ, which can be colonized by T lymphocyte progenitors and generate thymocytes that are selected by the T cell receptor repertoire following the positive and negative selection. However, CT and the main thoracic Thymus (TT) have been shown in mice to have significant Functional differences. In this study, we use transcriptional profiling to compare mRNA or miRNAs expression patterns in murine CT and TT. We used these data to perform Functional enrichment of the expression signatures and reconstruction of posttranscriptional miRNA-mRNA interaction networks. For this purpose, we compared the transcriptome profiling of paired RNA samples of whole CTs, TTs and parathyroid gland (PT), which was used as an external group, from Foxn1-GFP;Pth-Cre;R26dTomato transgenic mice that differentially label CT and TT. As expected, CT and TT featured comprehensive transcriptome similarity and this suggests that these organs are subjected to correlated transcriptional control. Nevertheless, significant differences were also observed between TT and CT, characterized by 107 differentially expressed (DE) mRNAs, and in 13 DE miRNAs, that in turn established interactions. These results suggest that Functional similarity between TT and CT is reflected in their transcriptional activity and that CT Functional uniqueness might be under posttranscriptional control.
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sublethal total body irradiation causes long term deficits in Thymus Function by reducing lymphoid progenitors
Journal of Immunology, 2017Co-Authors: Shiyun Xiao, Gregory D Sempowski, Ivo D Shterev, Wen Zhang, Lauren Young, Jaehung Shieh, Malcolm A S Moore, Marcel R M Van Den Brink, Nancy R ManleyAbstract: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.