Centre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway.
Cell Rep. 2013 Aug 15;4(3):566-77. doi: 10.1016/j.celrep.2013.07.011. Epub 2013 Aug 8.
There is increasing interest in the chronic lymphocytic leukemia (CLL) microenvironment and the mechanisms that may promote CLL cell survival and proliferation. A role for T helper (Th) cells has been suggested, but current evidence is only circumstantial. Here we show that CLL patients had memory Th cells that were specific for endogenous CLL antigens. These Th cells activated autologous CLL cell proliferation in vitro and in human → mouse xenograft experiments. Moreover, CLL cells were efficient antigen-presenting cells that could endocytose and process complex proteins through antigen uptake pathways, including the B cell receptor. Activation of CLL cells by Th cells was contact and CD40L dependent. The results suggest that CLL is driven by ongoing immune responses related to Th cell-CLL cell interaction. We propose that Th cells support malignant B cells and that they could be targeted in the treatment of CLL.
人们对慢性淋巴细胞白血病（CLL）微环境及其促进 CLL 细胞存活和增殖的机制越来越感兴趣。已经有人提出了辅助性 T 细胞（Th）的作用，但目前的证据只是间接的。在这里，我们发现 CLL 患者的记忆性 Th 细胞针对内源性 CLL 抗原具有特异性。这些 Th 细胞在体外和人源→鼠异种移植实验中激活了自身的 CLL 细胞增殖。此外，CLL 细胞是有效的抗原呈递细胞，可通过包括 B 细胞受体在内的抗原摄取途径内吞和加工复杂蛋白。Th 细胞通过细胞接触和 CD40L 依赖性激活 CLL 细胞。这些结果表明，CLL 是由与 Th 细胞-CLL 细胞相互作用相关的持续免疫反应驱动的。我们提出，Th 细胞支持恶性 B 细胞，并且它们可能成为 CLL 治疗的靶点。
