Chronic lymphocytic leukaemia (CLL) is associated with alterations in T cell number, subset distribution and function. Among these changes, an increase in CD4+ T cells was reported. CD4+ T cells are a heterogeneous population and distinct subsets have been described to exert pro- and anti-tumour functions. In CLL, controversial reports describing the dominance of IFNγ-expressing Th1 T cells or of IL-4-producing Th2 T cells exist. Our study shows that blood of CLL patients is enriched in Th1 T cells producing high amounts of IFNγ. Moreover, we observed that their frequency remains relatively stable in CLL patients over a time course of five years. Furthermore, we provide evidence for an accumulation of Th1 T cells in the Eµ-TCL1 mouse model of CLL. As TBET (encoded by Tbx21) is a crucial transcription factor for Th1 polarization, we generated Tbx21-/- bone marrow chimaeric mice which showed a lower number of IFNγ-producing Th1 T cells, and used them for adoptive transfer of Eµ-TCL1 leukaemia. Disease development in these mice was, however, comparable to that in wild-type controls, excluding a major role for TBET-expressing Th1 cells in Eµ-TCL1 leukaemia. Collectively, our data highlight that Th1 T cells accumulate in CLL but reducing their number has no impact on disease development.

中文翻译：

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表达TBET的Th1 CD4 + T细胞在慢性淋巴细胞性白血病中蓄积，而不会影响Eµ-TCL1小鼠的疾病进展。

慢性淋巴细胞性白血病（CLL）与T细胞数量，亚群分布和功能的改变有关。在这些变化中，据报道CD4 + T细胞增加。CD4 + T细胞是异质群体，并且已经描述了发挥亚肿瘤和抗肿瘤功能的不同亚群。在CLL中，存在有争议的报道，描述了表达IFNγ的Th1 T细胞或产生IL-4的Th2 T细胞的优势。我们的研究表明，CLL患者的血液中富含产生大量IFNγ的Th1 T细胞。此外，我们观察到他们的频率在CLL患者中保持五年时间相对稳定。此外，我们为CLL的Eµ-TCL1小鼠模型中Th1 T细胞的积累提供了证据。由于TBET（由Tbx21编码）是Th1极化的关键转录因子，我们生成了Tbx21-/-骨髓嵌合小鼠，这些小鼠显示出较少的产生IFNγ的Th1 T细胞数量，并用于过继转移Eµ-TCL1白血病。然而，这些小鼠的疾病发展与野生型对照相当，除了表达TBET的Th1细胞在Eµ-TCL1白血病中起主要作用。总体而言，我们的数据强调了Th1 T细胞在CLL中积累，但减少其数量对疾病的发展没有影响。