Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic.
CLIP - Childhood Leukaemia Investigation Prague, Czech Republic; Department of Pediatric Hematology, Charles University and Univ. Hospital Motol, Prague, Czech Republic.
Clin Immunol. 2023 Nov;256:109793. doi: 10.1016/j.clim.2023.109793. Epub 2023 Sep 28.
The aim of this study was to investigate the impact of thymic dysplasia on the phenotypic and functional characteristics of T cells in patients with 22q11.2 deletion syndrome, including T-cell phenotype, transcriptional profile, cytokine production, as well as the possibility of utilizing IL-7 to recover their numbers and function. We found a strong bias towards Th1 response in pediatric and young adult 22q11.2DS patients, expansion of CXCR5 follicular helper cells and CXCR3CCR6 Th1 cells, increased production of cytokines IFN-γ, IL-10, IL-2, IL-21 and TNF-α. This Th1 skew was primarily driven by expanded terminally differentiated T cells. IL-7 further reduced naive T cells, increased cytokine production and caused an upregulation of exhaustion markers. Thus, Th1 bias in T cell populations persists from infancy into adolescence and is accompanied by accelerated maturation of T cells into memory stages. This phenotype is exacerbated by IL-7 which causes further decrease in naïve T cells in vitro.
本研究旨在探讨胸腺发育不良对 22q11.2 缺失综合征患者 T 细胞表型和功能特征的影响，包括 T 细胞表型、转录谱、细胞因子产生，以及利用 IL-7 恢复其数量和功能的可能性。我们发现，儿科和年轻成年 22q11.2DS 患者存在强烈的 Th1 反应偏向，CXCR5 滤泡辅助细胞和 CXCR3CCR6 Th1 细胞扩增，IFN-γ、IL-10、IL-2、IL-21 和 TNF-α 细胞因子产生增加。这种 Th1 偏向主要是由终末分化 T 细胞扩增驱动的。IL-7 进一步减少了幼稚 T 细胞，增加了细胞因子的产生，并导致衰竭标志物的上调。因此，T 细胞群中的 Th1 偏向从婴儿期持续到青春期，并伴有 T 细胞向记忆阶段的加速成熟。IL-7 加剧了这种表型，导致体外幼稚 T 细胞进一步减少。
