PDF(Pubmed)
Abstract：
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.
摘要：
严重的血液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细胞的影响的知识非常有限。记忆T细胞在抵御疱疹病毒中起着至关重要的作用，这在儿科癌症护理中特别重要。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，一些人接受有或没有异基因造血干细胞移植（allo-HSCT）的BM抑制治疗，17个健康对照。我们使用流式细胞术专注于记忆T细胞亚群的外周血比例，并通过四参数FluoroSpot测定法分析了细胞因子分泌T细胞，以响应T细胞丝裂原和水痘带状疱疹病毒（VZV）肽。与健康对照相比,接受BM抑制治疗的患者显示分化(CD)4+和CD8+效应记忆(TEM)/终末分化效应(TEFF)T细胞簇增加。他们还展示了,除其他外，与健康对照相比，分泌细胞因子的细胞总数减少，通过干扰素（IFN）-γ，白细胞介素（IL）-17A，有丝分裂原激活后的IL-10和IL-22。在VZV肽刺激后，观察到BM抑制治疗儿童的IFN-γ反应减弱，与健康的孩子相比。总的来说，本文的研究结果表明，正在接受或已经完成BM抑制治疗的儿童在他们的T细胞记忆区表现出质的差异，可能会增加他们对严重病毒感染的易感性，并影响他们的免疫疗法，这依赖于自体T细胞的功能能力。
