CD8型
免疫学
移植物抗宿主病
细胞毒性T细胞
人口
造血
T细胞
医学
白血病
生物
抗原
免疫系统
疾病
病理
干细胞
细胞生物学
体外
遗传学
环境卫生
作者
Nicholas J Hess,David Turicek,Jeremiah Riendeau,Sean J. McIlwain,Emmanuel Contreras,Kalyan Nadiminti,Amy W. Hudson,Natalie S. Callander,Melissa C. Skala,Jenny E. Gumperz,Peiman Hematti,Christian M. Capitini
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-03-24
卷期号:9 (12)
被引量:1
标识
DOI:10.1126/sciadv.adf0567
摘要
An important paradigm in allogeneic hematopoietic cell transplantations (allo-HCTs) is the prevention of graft-versus-host disease (GVHD) while preserving the graft-versus-leukemia (GVL) activity of donor T cells. From an observational clinical study of adult allo-HCT recipients, we identified a CD4+/CD8+ double-positive T cell (DPT) population, not present in starting grafts, whose presence was predictive of ≥ grade 2 GVHD. Using an established xenogeneic transplant model, we reveal that the DPT population develops from antigen-stimulated CD8 T cells, which become transcriptionally, metabolically, and phenotypically distinct from single-positive CD4 and CD8 T cells. Isolated DPTs were sufficient to mediate xeno-GVHD pathology when retransplanted into naïve mice but provided no survival benefit when mice were challenged with a human B-ALL cell line. Overall, this study reveals human DPTs as a T cell population directly involved with GVHD pathology.
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