Thymus Reconstitution in Young and Aged Mice Is Facilitated by In Vitro-Generated Progenitor T Cells.
Thymus Reconstitution in Young and Aged Mice Is Facilitated by In Vitro-Generated Progenitor T Cells.
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DOI：
10.3389/fimmu.2022.926773
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
在化疗/放疗后接受造血干细胞移植（HSCT）的老年患者中，T细胞恢复的长期滞后可导致免疫功能障碍。因此，正在康复的病人可能会复发恶性肿瘤和机会性感染，导致高死亡率。T细胞恢复的延迟部分是由于胸腺退化（胸腺的大小和功能随着个体年龄的增长而自然萎缩），部分是由于胸腺基质细胞因暴露于化疗/放疗而遭受的损伤。在治疗老年患者时，显然需要新的策略来加速胸腺内T细胞重建，以对抗衰老和癌症治疗方案的影响。人类祖T （proT）细胞的过继转移已被证明可以加速放射治疗的年轻小鼠的T细胞再生，并恢复免疫缺陷小鼠的胸腺结构。在这里，我们证明，与单独的HSCT相比，在18-24个月的老年小鼠中，体外生成的proT细胞的过继转移加速了化疗和γ射线照射治疗后的胸腺重建。我们注意到，与年轻小鼠相比，尽管采用相同的化疗/放疗方案，老年小鼠的CD4-CD8胸腺细胞的扩增似乎更有限，供体T细胞向成熟T细胞发育的时间动力学也更慢。这表明年轻的胸腺比年老的胸腺更有弹性。然而，移植的老年和年轻小鼠的新生成的T细胞很容易出现在外周，加速了新的naïve T细胞的再现。在接受proT细胞和HSCT的老年和年轻小鼠中也观察到加速的T细胞恢复。移植proT细胞的策略可以作为一种有效的细胞疗法用于老年患者，以提高免疫恢复和降低hsct后机会性感染的风险。
The prolonged lag in T cell recovery seen in older patients undergoing hematopoietic stem cell transplant (HSCT), after chemo-/radiotherapy, can lead to immune dysfunction. As a result, recovering patients may experience a relapse in malignancies and opportunistic infections, leading to high mortality rates. The delay in T cell recovery is partly due to thymic involution, a natural collapse in the size and function of the thymus, as individuals age, and partly due to the damage sustained by the thymic stromal cells through exposure to chemo-/radiotherapy. There is a clear need for new strategies to accelerate intrathymic T cell reconstitution when treating aged patients to counter the effects of involution and cancer therapy regimens. Adoptive transfer of human progenitor T (proT) cells has been shown to accelerate T cell regeneration in radiation-treated young mice and to restore thymic architecture in immunodeficient mice. Here, we demonstrate that the adoptive transfer of in vitro-generated proT cells in aged mice (18-24 months) accelerated thymic reconstitution after treatment with chemotherapy and gamma irradiation compared to HSCT alone. We noted that aged mice appeared to have a more limited expansion of CD4-CD8- thymocytes and slower temporal kinetics in the development of donor proT cells into mature T cells, when compared to younger mice, despite following the same chemo/radiation regimen. This suggests a greater resilience of the young thymus compared to the aged thymus. Nevertheless, newly generated T cells from proT cell engrafted aged and young mice were readily present in the periphery accelerating the reappearance of new naïve T cells. Accelerated T cell recovery was also observed in both aged and young mice receiving both proT cells and HSCT. The strategy of transferring proT cells can potentially be used as an effective cellular therapy in aged patients to improve immune recovery and reduce the risk of opportunistic infections post-HSCT.
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DOI：
10.1186/1742-4933-5-1
发表时间：
2008-02-11
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Pinchuk LM;Filipov NM
通讯作者：
Filipov NM
影响因子：
8.8
作者：
Griffith AV;Venables T;Shi J;Farr A;van Remmen H;Szweda L;Fallahi M;Rabinovitch P;Petrie HT
通讯作者：
Petrie HT
影响因子：
7.8
作者：
Hernández L;Terradas M;Camps J;Martín M;Tusell L;Genescà A
通讯作者：
Genescà A
胸腺基质细胞：在胸腺萎缩和年龄相关功能障碍中的作用。
影响因子：
3.9
作者：
Cepeda S;Griffith AV
通讯作者：
Griffith AV
影响因子：
7.8
作者：
Aw, Danielle;Silva, Alberto B.;Palmer, Donald B.
通讯作者：
Palmer, Donald B.