Stai Stamatia, Lioulios Georgios, Xochelli Aliki, Papadopoulou Anastasia, Yannaki Evangelia, Kasimatis Efstratios, Christodoulou Michalis, Moysidou Eleni, Samali Margarita, Testa Theodolinda, Iosifidou Artemis Maria, Iosifidou Myrto Aikaterini, Tsoulfas Georgios, Stangou Maria, Fylaktou Asimina
School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
1st Department of Nephrology, Hippokration General Hospital, 54642 Thessaloniki, Greece.
Vaccines (Basel). 2024 Aug 2;12(8):877. doi: 10.3390/vaccines12080877.
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).
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, T, 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.
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, : 0.036], lower CD4+CD28- T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, : 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, : 0.04].
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.
多次接种疫苗对免疫系统衰老过程可能产生有害影响。我们研究了接受托珠单抗治疗的肾移植受者（KTRs）对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗接种的反应是否与免疫衰老和免疫耗竭有关。
在这项前瞻性观察研究中，我们观察了39名无抗SARS-CoV-2抗体且免疫抑制稳定的成年肾移植受者（KTRs）。在两个时间点评估CD4+和CD8+T细胞亚群[包括CD45RA+CCR7+（幼稚型）、CD45RA-CCR7+（中央记忆T细胞，TCM）、CD45RA-CCR7-（效应记忆T细胞，TEM）和CD45RA+CCR7-（重新表达CD45RA的效应记忆T细胞，T，衰老型）、CD28-（衰老型）和PD1+（耗竭型）]：T1（第3剂之前48小时）和T2（第3剂托珠单抗给药后3周）。在每个时间点，将患者分为体液和/或细胞应答者和无应答者。
从T1到T2，整个患者队列中CD4+TCM和CD8+TEM增加，而幼稚型CD4+和CD8+比例降低，在应答者中更为明显。在T2时，与无应答者相比，应答者的CD8+CD28+更高[227.15（166）对131.44（121）个细胞/μL，：0.036]，CD4+CD28-T淋巴细胞数量更低[59.65（66）个细胞/μL对161.19（92）个细胞/μL，：0.026]和百分比更低[6.1（5.5）%对20.7（25）%，：0.04]。
在肾移植受者中，疫苗接种反应与衰老和耗竭T细胞浓度的增加无关，而是与从幼稚型T细胞形式向分化激活型T细胞形式的转变有关。
