Chronic lymphocytic leukaemia (CLL) patients often have abnormal expansions of CD4+ and CD8+ T cells and this can be associated with progressive disease. To characterise the key T-cell populations involved in this phenomenon, we used flow cytometry and 11 phenotypic markers to study 74 CLL patients and 14 controls. T cells of CLL patients were more phenotypically complex than those of healthy controls with significant increases in the frequencies of CD4 and CD8 memory T cells expressing exhaustion-, activation- and senescence-associated markers. Multivariate analysis of 111 different T-cell subsets showed that high frequencies of four subsets (three CD8 and one CD4) were associated with shorter progression-free survival. The most significant association was with CD4+ HLA-DR+ PD-1+ T cells, and patients could be stratified into high- and low-risk groups based on the frequency of these T cells. The expansion of this CD4+ subset could not be accounted for by age, cytomegalovirus infection or increases in Treg cells. Overall, these results highlight two relatively simple biomarkers, percentage CD8+ and percentage CD4+ PD-1+ HLA-DR+ T cells, which can be used to risk-stratify CLL patients, independent of other tumour-associated markers. They also provide further evidence for the pivotal role of T cells in modulating the pathology of CLL.

中文翻译：

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CD4+ PD-1+ HLA-DR+ T 细胞频率增加与 CLL 疾病进展相关。


慢性淋巴细胞白血病 (CLL) 患者通常存在 CD4+ 和 CD8+ T 细胞的异常扩增，这可能与疾病进展有关。为了表征参与这种现象的关键 T 细胞群，我们使用流式细胞术和 11 个表型标记物研究了 74 名 CLL 患者和 14 名对照者。 CLL 患者的 T 细胞表型比健康对照更复杂，表达耗竭、激活和衰老相关标记物的 CD4 和 CD8 记忆 T 细胞的频率显着增加。对 111 个不同 T 细胞亚群的多变量分析表明，四个亚群（三个 CD8 和一个 CD4）的高频率与较短的无进展生存期相关。最显着的关联是 CD4+ HLA-DR+ PD-1+ T 细胞，并且可以根据这些 T 细胞的频率将患者分为高风险组和低风险组。这种 CD4+ 亚群的扩张不能用年龄、巨细胞病毒感染或 Treg 细胞的增加来解释。总体而言，这些结果突出了两种相对简单的生物标志物，即 CD8+ 百分比和 CD4+ PD-1+ HLA-DR+ T 细胞百分比，它们可用于对 CLL 患者进行风险分层，独立于其他肿瘤相关标志物。他们还为 T 细胞在调节 CLL 病理学中的关键作用提供了进一步的证据。