T cell response to CD200+/- acute myeloid leukemia

Purpose: Understanding immunosuppression in AML is critical . The goals of this study are to compare the transcriptomics of human CD3+ T cells from humanized mice exposed to CD200+/- AML. Methods: NSG mice were humanized with 10x10^6 healthy PBMCs prior to the introduction of CD200+ or CD200- OCI-AML3 cells. After 10 days, CD3+ T cells were isolated and RNA was sequenced. Results: T cells from mice with CD200+ AML were characterized by an enrichment of T cell activation pathways and a downregulation of numerous metabolic pathways, including OXPHOS and glycolysis. Conclusions: Our results demonstrate, for the first time, that CD200+ AML can directly impair T cell metbolism. Overall design: RNA-seq analysis of sorted CD3+ human T cells extracted from PBMC-humanized mice with either CD200+ (n=3), CD200- (n=3) OCI-AML3 leukemia, or controls (n=2). Results provide insight into the mechanisms of CD200 immunosuppression.研究目的：明确急性髓系白血病（Acute Myeloid Leukemia, AML）中的免疫抑制机制具有关键临床价值。本研究旨在对比暴露于CD200阳性/阴性（CD200+/-）AML的人源化小鼠（humanized mice）体内分离的人源CD3阳性T细胞（CD3+ T cells）的转录组学特征。 实验方法：先以10×10^6个健康外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMC）对NSG小鼠进行人源化改造，随后分别接种CD200阳性或CD200阴性的OCI-AML3细胞。接种10天后，分离CD3+ T细胞并开展RNA测序。 实验结果：携带CD200阳性AML的小鼠体内T细胞具有两大特征：T细胞活化通路显著富集，而包括氧化磷酸化（Oxidative Phosphorylation, OXPHOS）与糖酵解在内的多条代谢通路则出现表达下调。 研究结论：本研究首次证实，CD200阳性AML可直接损害T细胞代谢功能。 实验整体设计：对来自三组PBMC人源化小鼠的分选CD3+人源T细胞进行RNA测序分析，三组分别为：CD200阳性OCI-AML3白血病组（n=3）、CD200阴性OCI-AML3白血病组（n=3）以及对照组（n=2）。本研究结果为解析CD200介导的免疫抑制机制提供了重要见解。