CD5-expressing CD8+ T-cell subsets differ between children with type 1 diabetes and controls,Immunology and Cell Biology

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CD5-expressing CD8+ T-cell subsets differ between children with type 1 diabetes and controls
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2021-06-16 , DOI: 10.1111/imcb.12488
Josefine Wadenpohl ₁ , Julia Seyfarth ₁ , Paul Hehenkamp ₁ , Maximilian Hoffmann ₁ , Sebastian Kummer ₁ , Christina Reinauer ₁ , Carsten Döing ₁ , Katharina Förtsch ₁ , Ertan Mayatepek ₁ , Thomas Meissner ₁ , Marc Jacobsen ₁

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Different lymphocyte subsets are involved in autoimmune pathogenesis of type 1 diabetes (T1D). Previous studies suggested a role of CD5-expressing T and B cells including rare unconventional lymphocytes with combined T- and B-cell features [dual expressing (DE) cells]. We performed algorithm-supported multiparameter flow cytometry and quantitative PCR to investigate immune cell subsets and DE cells in children with T1D (n = 20) and matched controls (n = 20). Comparisons of conventional immune cells detected increased proportions of CD3⁺ T cells in T1D patients, whereas CD19⁺ B-cell proportions were comparable to controls. Self-organizing maps for flow cytometry analyses (FlowSOM) showed highly similar CD5-expressing B-cell subsets and no differences for DE cells were detected between the study groups by flow cytometry or specific quantitative PCR. Notably, differences in CD8⁺ T cells were indicated by FlowSOM and similarity-based t-distributed stochastic neighbor embedding (tSNE) analyses. Study group comparisons confirmed significantly reduced CD8⁺ T-cell proportions with moderate or low CD5 expression in T1D patients. Finally, in vitro experiments showed stable CD5 expression differences of CD8⁺ T cells after T-cell activation, cytokine stimulation and culture. We observed differences of T-cell coreceptor CD5 expression in T1D patients with potential relevance for immune regulation of CD8⁺ T-cell activation.

中文翻译：

1 型糖尿病儿童和对照组之间表达 CD5 的 CD8+ T 细胞亚群不同

不同的淋巴细胞亚群参与 1 型糖尿病 (T1D) 的自身免疫发病机制。以前的研究表明表达 CD5 的 T 和 B 细胞的作用，包括具有组合 T 和 B 细胞特征的罕见非常规淋巴细胞 [双重表达 (DE) 细胞]。我们进行了算法支持的多参数流式细胞术和定量 PCR，以研究 T1D 儿童 ( n = 20) 和匹配对照 ( n = 20) 的免疫细胞亚群和 DE 细胞。传统免疫细胞的比较检测到T1D 患者中 CD3 ⁺ T 细胞的比例增加，而 CD19 ⁺B 细胞比例与对照相当。用于流式细胞术分析 (FlowSOM) 的自组织图谱显示出高度相似的表达 CD5 的 B 细胞亚群，并且通过流式细胞术或特异性定量 PCR 在研究组之间未检测到 DE 细胞的差异。值得注意的是，FlowSOM 和基于相似性的 t 分布随机邻域嵌入 (tSNE) 分析表明了CD8 ⁺ T 细胞的差异。研究组比较证实，在 T1D 患者中，CD8 ⁺ T 细胞比例显着降低，CD5 表达中度或低度。最后，体外实验表明CD8 ^+的稳定CD5表达差异T 细胞活化、细胞因子刺激和培养后的 T 细胞。我们观察到 T1D 患者中 T 细胞辅助受体 CD5 表达的差异，这与 CD8 ⁺ T 细胞活化的免疫调节具有潜在相关性。

更新日期：2021-06-16

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