背景:多次接种疫苗对免疫系统衰老过程具有潜在的有害影响。我们检查了用Tozinameran接种SARS-CoV-2疫苗的反应是否与肾移植受者(KTR)的免疫衰老和免疫衰竭有关。
方法:在这项前瞻性观察研究中,我们观察了39例成人肾移植受者(KTRs),这些受者没有预先存在的抗SARS-CoV-2抗体,并且有稳定的免疫抑制.CD4+和CD8+T细胞亚群[包括CD45RA+CCR7+(初始),CD45RA-CCR7+(T型中央存储器,TCM),CD45RA-CCR7-(T效应子记忆,TEM)和CD45RA+CCR7-(T-效应记忆再表达CD45RA,TEMRA,衰老),在2个时间点评估CD28-(衰老)和PD1(耗尽)]:T1(第3个之前48小时),和T2(第3次Tozinameran剂量给药后3周)。在每个时间点,患者被分为体液和/或细胞反应者和非反应者。
结果:从T1到T2,CD4+TCM和CD8+TEM升高,而在整个患者队列中,初始CD4+和CD8+比例降低,在响应者中更突出。在T2时,响应者与非响应者相比具有更高的CD8+CD28+[227.15(166)与131.44(121)个细胞/微升,p:0.036],较低的CD4+CD28-T淋巴细胞数量[59.65(66)细胞/μLvs.161.19(92)个细胞/微升,p:0.026]和百分比[6.1(5.5)%vs.20.7(25)%,P:0.04]。
结论:在KTR中,对疫苗接种的反应与衰老和耗尽的T细胞浓度的增加无关,而是从幼稚到分化激活的T细胞形式的转变。
BACKGROUND: Multiple vaccinations have potential inimical effects on the immune system aging process. We examined whether response to SARS-CoV-2 vaccination with Tozinameran is associated with immunosenescence and immunoexhaustion in kidney transplant recipients (KTRs).
METHODS: In this prospective observational study, we observed 39 adult kidney transplant recipients (KTRs) who had no pre-existing anti-SARS-CoV-2 antibodies and were on stable immunosuppression. CD4+ and CD8+ T-cell subpopulations [comprising CD45RA+CCR7+ (naïve), CD45RA-CCR7+ (T-central memory, TCM), CD45RA-CCR7- (T-effector memory, TEM) and CD45RA+CCR7- (T-effector memory re-expressing CD45RA, TEMRA, senescent), CD28- (senescent) and PD1+ (exhausted)] were evaluated at 2 time points: T1 (48 h prior to the 3rd), and T2 (3 weeks following the 3rd Tozinameran dose administration). At each time point, patients were separated into Humoral and/or Cellular Responders and Non-Responders.
RESULTS: From T1 to T2, CD4+TCM and CD8+TEM were increased, while naïve CD4+ and CD8+ proportions were reduced in the whole cohort of patients, more prominently among responders. At T2, responders compared to non-responders had higher CD8+CD28+ [227.15 (166) vs. 131.44 (121) cells/µL, p: 0.036], lower CD4+CD28- T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, p: 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, p: 0.04].
CONCLUSIONS: In KTRs, response to vaccination is not associated with an expansion of senescent and exhausted T-cell concentrations, but rather with a switch from naïve to differentiated-activated T-cell forms.