Cancer Immunol Immunother. 2013 Nov;62(11):1697-1709. doi: 10.1007/s00262-013-1473-z.
Altered numbers and functions of T cells have previously been demonstrated in chronic lymphocytic leukemia (CLL) patients. However, dynamics and specific T-cell subset alterations have not been studied in great detail. Therefore, we studied CLL blood lymphocyte subsets of individual patients in a longitudinal manner. Dynamic expansions of blood CD4 + and CD8 + T-cell numbers were consistently associated with a progressively increasing CLL leukemic compartment. Interestingly, the T-cell subset expansion over time was more pronounced in CD38 + CLL. Additionally, we performed gene expression profiling of CD3 + T cells of CLL patients and normal donors. Using gene set enrichment analysis, we found significant enrichment of genes with higher expression in CLL T cells within CD8+ effector memory and terminal effector T-cell gene signatures. In agreement with these data, we observed a marked expansion of phenotypic CD8 + effector memory T cells in CLL by flow cytometry. Moreover, we observed that increments of CD8 + effector memory T cells in human CLL and also mouse CLL (Eμ-TCL1 model) were due to an expansion of the inhibitory killer cell lectin-like receptor G1 (KLRG1) expressing cellular subset. Furthermore, higher plasma levels of the natural KLRG1 ligand E-cadherin were detected in CLL patients compared to normal donor controls. The predominance of KLRG1+ expression within CD8+ T cells in conjunction with increased systemic soluble E-cadherin might significantly contribute to CLL immune dysfunction and might additionally represent an important component of the CLL microenvironment.
先前已经证明，慢性淋巴细胞白血病（CLL）患者的 T 细胞数量和功能发生了改变。然而，尚未详细研究 CLL 患者血液淋巴细胞亚群的动态变化和特定 T 细胞亚群的改变。因此，我们对个体患者的 CLL 血液淋巴细胞亚群进行了纵向研究。血液 CD4+和 CD8+T 细胞数量的动态扩张与 CLL 白血病细胞区室的逐渐增加一致相关。有趣的是，CD38+CLL 中 T 细胞亚群的扩张随时间推移更为明显。此外，我们对 CLL 患者和正常供体的 CD3+T 细胞进行了基因表达谱分析。通过基因集富集分析，我们发现 CLL T 细胞中具有更高表达的基因在 CD8+效应记忆和终末效应 T 细胞基因特征内显著富集。与这些数据一致，我们通过流式细胞术观察到 CLL 中表型 CD8+效应记忆 T 细胞的显著扩张。此外，我们观察到人类 CLL 和小鼠 CLL（Eμ-TCL1 模型）中 CD8+效应记忆 T 细胞的增加是由于抑制性杀伤细胞凝集素样受体 G1（KLRG1）表达细胞亚群的扩张所致。此外，与正常供体对照相比，CLL 患者的血浆中检测到更高水平的天然 KLRG1 配体 E-钙粘蛋白。CD8+T 细胞内 KLRG1+表达的优势以及系统性可溶性 E-钙粘蛋白的增加可能显著导致 CLL 免疫功能障碍，并且可能另外代表 CLL 微环境的一个重要组成部分。
