Betjes Michiel G H, Langerak Anton W, Klepper Mariska, Litjens Nicolle H R
1Department of Internal Medicine, section Nephrology and Transplantation, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
2Department of Immunology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
Immun Ageing. 2020 Feb 13;17:4. doi: 10.1186/s12979-020-00175-z. eCollection 2020.
End-stage renal disease is associated with premature ageing of the T cell immune system but inter-individual variation is substantial. The hypothesis was tested that advanced immunological T cell ageing assessed by peripheral T cell differentiation increases the long-term mortality risk after renal transplantation.
Circulating T cells of 211 recipients of a kidney from a living donor were analyzed before and in the first year after transplantation. The number of CD31-positive naive T cells (as a marker for recent thymic emigrants) and the differentiation status of the memory T cells was assessed. Thirty recipients died during follow-up of at least 5 years. Absolute numbers of naive CD4 (living:258 cells/μl vs. deceased:101 cells/μl, < 0.001) and naive CD8 T cells (living:97 cells/μl vs. deceased:37 cells/μl, p < 0.001) were significantly lower in the deceased group prior to transplantation. In a multivariate proportional hazard analysis the number of naive CD4 T cells remained associated with all-cause mortality (HR 0.98, CI 0.98-0.99, < 0.001). The low number of naive T cells in the deceased patient group was primarily caused by a decrease in recent thymic emigrants (i.e. less CD31 naive T cells) indicating a lowered thymus function. In addition, the physiological age-related compensatory increase in CD31 naïve T cells was not observed. Within the first year after transplantation, the number and characteristics of naive T cells remained stable.
A severe reduction in circulating naïve T cells because of a decrease in recent thymic emigrants is highly associated with all-cause mortality after renal transplantation.
终末期肾病与T细胞免疫系统过早老化相关,但个体间差异很大。本研究检验了如下假设:通过外周T细胞分化评估的T细胞免疫高级老化会增加肾移植后的长期死亡风险。
对211例活体供肾受者移植前及移植后第一年的循环T细胞进行了分析。评估了CD31阳性幼稚T细胞数量(作为近期胸腺迁出细胞的标志物)和记忆T细胞的分化状态。30例受者在至少5年的随访期间死亡。移植前,死亡组的幼稚CD4 T细胞绝对数量(存活者:258个细胞/μl,死亡者:101个细胞/μl,<0.001)和幼稚CD8 T细胞绝对数量(存活者:97个细胞/μl,死亡者:37个细胞/μl,p<0.001)显著低于存活组。在多变量比例风险分析中,幼稚CD4 T细胞数量仍与全因死亡率相关(风险比0.98,置信区间0.98 - 0.99,<0.001)。死亡患者组中幼稚T细胞数量低主要是由于近期胸腺迁出细胞减少(即CD31阳性幼稚T细胞减少),表明胸腺功能降低。此外,未观察到与生理年龄相关的CD31阳性幼稚T细胞代偿性增加。移植后第一年内,幼稚T细胞的数量和特征保持稳定。
由于近期胸腺迁出细胞减少导致循环幼稚T细胞严重减少与肾移植后的全因死亡率高度相关。