免疫系统
免疫学
髓样
造血干细胞移植
细胞疗法
医学
移植物抗宿主病
归巢(生物学)
移植
干细胞
生物
内科学
生态学
遗传学
作者
Astrid G. S. van Halteren,Jessica S. Suwandi,Sander Tuit,Jannie Borst,Sandra Laban,Roula Tsonaka,Ada C Struijk,Anna-Sophia Wiekmeijer,Melissa van Pel,Bart O. Roep,Jaap Jan Zwaginga,Arjan C. Lankester,Koen Schepers,Maarten J. D. van Tol,Willem E. Fibbe
出处
期刊:Blood
[American Society of Hematology]
日期:2023-03-16
卷期号:141 (11): 1277-1292
标识
DOI:10.1182/blood.2022015734
摘要
Acute graft-versus-host disease (aGVHD) is an immune cell‒driven, potentially lethal complication of allogeneic hematopoietic stem cell transplantation affecting diverse organs, including the skin, liver, and gastrointestinal (GI) tract. We applied mass cytometry (CyTOF) to dissect circulating myeloid and lymphoid cells in children with severe (grade III-IV) aGVHD treated with immune suppressive drugs alone (first-line therapy) or in combination with mesenchymal stromal cells (MSCs; second-line therapy). These results were compared with CyTOF data generated in children who underwent transplantation with no aGVHD or age-matched healthy control participants. Onset of aGVHD was associated with the appearance of CD11b+CD163+ myeloid cells in the blood and accumulation in the skin and GI tract. Distinct T-cell populations, including TCRγδ+ cells, expressing activation markers and chemokine receptors guiding homing to the skin and GI tract were found in the same blood samples. CXCR3+ T cells released inflammation-promoting factors after overnight stimulation. These results indicate that lymphoid and myeloid compartments are triggered at aGVHD onset. Immunoglobulin M (IgM) presumably class switched, plasmablasts, and 2 distinct CD11b- dendritic cell subsets were other prominent immune populations found early during the course of aGVHD in patients refractory to both first- and second-line (MSC-based) therapy. In these nonresponding patients, effector and regulatory T cells with skin- or gut-homing receptors also remained proportionally high over time, whereas their frequencies declined in therapy responders. Our results underscore the additive value of high-dimensional immune cell profiling for clinical response evaluation, which may assist timely decision-making in the management of severe aGVHD.
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