儿童骨髓抑制治疗与多克隆和水痘带状疱疹病毒肽刺激后 T 细胞的 IFN-γ 反应减弱有关。
Bone Marrow-Suppressive Treatment in Children Is Associated with Diminished IFN-γ Response from T Cells upon Polyclonal and Varicella Zoster Virus Peptide Stimulation.
发表日期:2024 Jun 26
作者:
Eva Tiselius, Emil Sundberg, Hanna Andersson, Anna Höbinger, Peter Jahnmatz, Arja Harila, Josefine Palle, Anna Nilsson, Shanie Saghafian-Hedengren
来源:
Stem Cell Research & Therapy
摘要:
严重的血液疾病和淋巴恶性肿瘤需要骨髓(BM)抑制治疗。关于 BM 抑制治疗对儿童记忆 T 细胞影响的知识非常有限。记忆 T 细胞在防御疱疹病毒方面发挥着至关重要的作用,这在儿科癌症护理中尤其重要。我们总共研究了 53 名儿童; 34 名患有癌症,2 名患有严重血液疾病,其中一些人接受了 BM 抑制治疗,有或没有同种异体造血干细胞移植 (allo-HSCT),还有 17 名健康对照。我们使用流式细胞术重点关注记忆 T 细胞亚群的外周血比例,并使用四参数 FluoroSpot 测定分析细胞因子分泌 T 细胞对 T 细胞有丝分裂原和水痘带状疱疹病毒 (VZV) 肽的反应。与健康对照相比,接受 BM 抑制治疗的患者表现出分化 (CD)4 和 CD8 效应记忆 (TEM)/终末分化效应 (TEFF) T 细胞簇增加。除其他外,与健康对照相比,通过干扰素 (IFN)-γ、白细胞介素 (IL)-17A、IL-10 和 IL-22,他们还表现出细胞因子分泌细胞总数减少。 ,在有丝分裂原激活后。与健康儿童相比,在接受 BM 抑制治疗的儿童中,在 VZV 肽刺激后观察到 IFN-γ 反应减弱。总的来说,本文的研究结果表明,正在接受或已经完成 BM 抑制治疗的儿童在其 T 细胞记忆区室中表现出质的差异,可能会增加他们对严重病毒感染的易感性并影响他们的免疫治疗,而免疫治疗依赖于 T 细胞的功能能力。自体T细胞。
Severe haematological diseases and lymphoid malignancies require bone marrow (BM)-suppressive treatments. Knowledge regarding the impact of BM-suppressive treatments on children's memory T cells is very limited. Memory T cells play a crucial role in defending against herpesviruses, which is particularly relevant in paediatric cancer care. We studied 53 children in total; 34 with cancer and 2 with severe haematological disorders, with some receiving BM-suppressive treatment with or without allogeneic-haematopoietic stem cell transplantation (allo-HSCT), alongside 17 healthy controls. We focused on peripheral blood proportions of memory T-cell subsets using flow cytometry and analysed cytokine-secreting T cells with a four-parameter FluoroSpot assay in response to T-cell mitogen and varicella zoster virus (VZV) peptides. Patients on BM-suppressive treatment showed increased clusters of differentiation (CD)4+ and CD8+ effector memory (TEM)/terminally differentiated effector (TEFF) T cells compared to the healthy controls. They also exhibited, amongst other things, when compared to the healthy controls, a reduced total number of cytokine-secreting cells, by means of interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-22, following mitogen activation. A diminished IFN-γ response among the children with BM-suppressive treatment was observed upon VZV-peptide stimulation, compared to the healthy children. Collectively, the findings herein indicate that the children who are undergoing or have finished BM-suppressive treatment display qualitative differences in their T-cell memory compartment, potentially increasing their susceptibility to severe viral infections and impacting their immunotherapy, which relies on the functional ability of autologous T cells.