National Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Copenhagen, Denmark.
Institute of Inflammatory Research, Rigshospitalet, Copenhagen, Denmark.
Front Immunol. 2024 Jan 10;14:1327977. doi: 10.3389/fimmu.2023.1327977. eCollection 2023.
Recovery and functional differentiation of T-cell subsets are central for the development of immune function and complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about the cellular respiration and factors influencing T-cell metabolic fitness during immune maturation after HSCT.
We included 20 HSCT patients and analysed mitochondrial oxidative phosphorylation and mitochondrial fitness in peripheral blood mononuclear cell samples collected at days +90 and +180 after HSCT.
Phenotypic analysis revealed lower overall T-cell counts, lower CD4+/CD8+ ratio and a skewed distribution of early T-cell subsets at day +90, gradually recovering by day +180. Although ATP turnover in HSCT patients was similar to healthy controls, the spare respiratory capacity (SRC) of T cells, reflecting the available energy reserve, was significantly reduced at day +90 and +180 compared to healthy controls. This reduction in SRC was not correlated with the occurrence of acute graft-versus-host disease (aGVHD), the intensity of conditioning regimens and markers of T-cell exhaustion.
We found significantly depressed SRC until six months post-HSCT, but we were not able to identify transplant-related risk factors or associations with the clinical outcome.
T 细胞亚群的恢复和功能分化是异体造血干细胞移植(HSCT)后免疫功能和并发症发展的核心,但对于 HSCT 后免疫成熟过程中 T 细胞代谢适应性的细胞呼吸和影响因素知之甚少。
我们纳入了 20 例 HSCT 患者,并分析了 HSCT 后第 90 天和第 180 天采集的外周血单个核细胞样本中的线粒体氧化磷酸化和线粒体适应性。
表型分析显示,HSCT 患者在第 90 天的总 T 细胞计数较低,CD4+/CD8+比值较低,早期 T 细胞亚群分布偏斜,到第 180 天逐渐恢复。尽管 HSCT 患者的 ATP 周转率与健康对照组相似,但 T 细胞的备用呼吸能力(SRC),反映了可用的能量储备,在第 90 天和第 180 天明显低于健康对照组。SRC 的降低与急性移植物抗宿主病(aGVHD)的发生、预处理方案的强度以及 T 细胞耗竭的标志物均无关。
我们发现 HSCT 后 6 个月 SRC 明显降低,但我们未能确定与移植相关的风险因素或与临床结果的关联。