Mechanisms of thymic recovery and T cell reconstitution following sublethal ionizing radiation (104.21)
| Autor: | Zana Këpuska, Gregory Sempowski |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:104.21-104.21 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.104.21 |
| Popis: | Proper thymic function is important for maintaining lifelong peripheral homeostasis of naïve and memory T cells. Age-induced thymic involution is chronic and does not recover. Acute thymus involution in settings of stress can spontaneously recover. The goal of this research was to define mechanisms of thymic damage and recovery following acute stress (irradiation). Young and old BALB/c mice were sublethaly irradiated (≤ 125 rad).Thymus function was monitored by thymus weight, cellularity, and TCR gene re-arrangement (mTREC). In young, irradiation significantly reduced thymocyte number and depleted mTREC levels by day 7, followed by full recovery (day 42). In old, radiation did not cause further decrease in thymocyte number or mTREC compared to that induced by age. To define mechanisms of thymic involution/recovery expression of thymostimulatory factors and indicators of healthy thymus were analyzed.While IL-7 and FoxN1 mRNA levels were not impacted in the young, KGF and AIRE mRNA expression levels were significantly reduced during irradiation-induced involution. These levels restored to baseline 21 days prior to full thymus functional recovery. Thus, suggesting a critical role of thymic-stromal derived KGF in promoting stroma/thymocyte crosstalk to mediate thymus recovery. Overall, these findings may lead to a better understanding of mechanisms involved in thymus recovery from damage and inform development of strategies to restore thymic function in the aged. |
| Databáze: | OpenAIRE |
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