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化疗诱导淋巴细胞减少后成人的年龄相关胸腺活性。

Age-related thymic activity in adults following chemotherapy-induced lymphopenia.

作者信息

Sfikakis P P, Gourgoulis G M, Moulopoulos L A, Kouvatseas G, Theofilopoulos A N, Dimopoulos M A

机构信息

Athens University Medical School, Athens, Greece.

出版信息

Eur J Clin Invest. 2005 Jun;35(6):380-7. doi: 10.1111/j.1365-2362.2005.01499.x.

DOI:10.1111/j.1365-2362.2005.01499.x
PMID:15948899
Abstract

BACKGROUND

The potential role of the adult thymus in T-cell homeostasis subsequent to lymphopenia remains the subject of debate. We examined whether thymic activity contributes to reconstitution of the peripheral T-cell pool, a critical process for patients recovering from antineoplastic therapy.

METHODS

In selected patients with various neoplastic diseases we assessed peripheral blood lymphocyte subsets by flow-cytometry, including thymus-derived, CD4+ T cells expressing the CD45RA molecule, and thymic size rebound by CT scan before, and 3, 6 and 12 months after completion of cytotoxic therapy.

RESULTS

Adult patients (n = 21, mean age of 30 years, range 18-49) had higher baseline numbers of B and lower numbers of NK cells than elderly patients (n = 15, mean age of 79 years, range 70-91), while total T-cell numbers did not differ. Despite the reduction of lymphocyte counts being comparable in the adult (mean of 45%) and elderly (mean of 49%) groups, occurring at, or near, completion of treatment, an enlargement of the previously atrophic thymus was evident in 63% of the adult, but in none of the elderly, subjects. In 22 patients who remained active disease-free during the following year, B cells and NK cells recovered to pretreatment levels as soon as at 3 months, whereas overall T-cell recovery occurred at 6 months post-treatment. Thymic rebound, observed in 11 of 22 patients who were of younger age, correlated significantly with a faster and more complete recovery of CD45RA+ CD4+ (mainly helper-naïve) T cells.

CONCLUSION

The adult thymus appears capable of regeneration, at least up to middle age, contributing significantly to the reconstitution of the peripheral T-cell pool following chemotherapy-induced lymphopenia. In advanced age, however, although peripheral homeostatic pathways appear intact, regeneration of the naïve repertoire is incomplete.

摘要

背景

成年胸腺在淋巴细胞减少后T细胞稳态中的潜在作用仍是一个有争议的话题。我们研究了胸腺活性是否有助于外周T细胞库的重建,这是肿瘤患者从抗肿瘤治疗中恢复的关键过程。

方法

在选定的患有各种肿瘤疾病的患者中,我们通过流式细胞术评估外周血淋巴细胞亚群,包括胸腺来源的、表达CD45RA分子的CD4+ T细胞,并在细胞毒性治疗前、治疗完成后3、6和12个月通过CT扫描评估胸腺大小的反弹情况。

结果

成年患者(n = 21,平均年龄30岁,范围18 - 49岁)的B细胞基线数量高于老年患者(n = 15,平均年龄79岁,范围70 - 91岁),NK细胞数量低于老年患者,而总T细胞数量无差异。尽管成年组(平均减少45%)和老年组(平均减少49%)的淋巴细胞计数在治疗结束时或接近治疗结束时减少程度相当,但63%的成年患者先前萎缩的胸腺明显增大,而老年患者中无一例出现这种情况。在随后一年保持无疾病活动的22例患者中,B细胞和NK细胞在3个月时就恢复到治疗前水平,而总体T细胞在治疗后6个月恢复。在22例较年轻的患者中有11例观察到胸腺反弹,这与CD45RA+ CD4+(主要是初始辅助)T细胞更快、更完全的恢复显著相关。

结论

成年胸腺似乎能够再生,至少到中年,这对化疗诱导的淋巴细胞减少后外周T细胞库的重建有显著贡献。然而,在老年时,尽管外周稳态途径似乎完整,但初始库的再生并不完全。

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