Withdrawal of Sex Steroids Reverses Age- and Chemotherapy-Related Defects in Bone Marrow Lymphopoiesis
Withdrawal of Sex Steroids Reverses Age- and Chemotherapy-Related Defects in Bone Marrow Lymphopoiesis
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DOI：
10.4049/jimmunol.0802446
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发表时间：
2009-05-15
影响因子：
4.4
通讯作者：
Boyd, Richard L.
中科院分区：
文献类型：
--
作者：
Dudakov, Jarrod A.;Goldberg, Gabrielle L.;Boyd, Richard L.
免疫功能的显著下降是衰老的特征。随着胸腺的退化和相关的结构受损，导致幼稚T细胞产生的严重损失，B细胞发育和支持淋巴生成的祖细胞也显著下降。这些共同导致外周免疫库减少，机会性感染增加，通过化疗或放疗进行细胞消融后恢复有限。我们之前的研究表明，性类固醇消融术（SSA）可以逆转与年龄相关的胸腺萎缩，并改善造血干细胞移植后的恢复。本研究主要研究了SSA对中年小鼠和环磷酰胺处理小鼠B细胞室及其祖细胞的影响。在这两种模型中，SSA增加了骨髓中淋巴样祖细胞和发育中的B细胞的数量，并逆转了这些细胞循环动力学中与年龄相关的缺陷。髓质淋巴生成增强反映在外周近期髓质移入以及未成熟和成熟浆细胞的增加，导致对乙型肝炎疫苗攻击的不道德反应增强。综上所述，SSA可以促进淋巴样祖细胞和R细胞从年龄和化疗诱导的免疫缺失中恢复，补充对T细胞的作用。由于SSA在临床上已经实现了超过25年，这为在许多临床条件下接近免疫恢复的需要提供了一个新的、合理的基础。免疫学杂志，2009,32(2):6247-6260。
A significant decline in immune function is characteristic of aging. Along with the involution of the thymus and associated impaired architecture, which contributes to profound loss of naive T cell production, there are also significant declines in B cell development and the progenitors that support lymphopoiesis. These collectively lead to a reduced peripheral immune repertoire, increase in opportunistic infections, and limited recovery following cytoablation through chemo- or radiotherapy. We have previously shown that sex steroid ablation (SSA) causes a major reversal of age-related thymic atrophy and improves recovery from hematopoietic stem cell transplant. This study focused on the impact of SSA on the B cell compartment and their progenitors in middle-aged and cyclophosphamide-treated mice. In both models, SSA enhanced the number of lymphoid progenitors and developing B cells in the bone marrow (BM) as well as reversing age-related defects in the cycling kinetics of these cells. Enhanced BM lymphopoiesis was reflected in the periphery by an increase in recent BM emigrants as well as immature and mature plasma cells, leading to an enhanced Immoral response to challenge by hepatitis B vaccine. In conclusion, SSA improves lymphoid progenitor and R cell recovery from age- and chemotherapy-induced immunodepletion, complimenting the effects on T cells. Since SSA has been achieved clinically for over 25 years, this provides a novel, rational basis for approaching the need for immune recovery in many clinical conditions. The Journal of Immunology, 2009, 182: 6247-6260.