Department of Immunology, Imperial College, Norfolk Place, London UK.
Adv Cancer Res. 2011;111:163-82. doi: 10.1016/B978-0-12-385524-4.00004-0.
Human T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukaemia/lymphoma (ATLL) in ∼5% of HTLV-1-infected people. ATLL cells frequently express several molecules that are characteristic of regulatory T cells (Tregs), notably CD4, CD25 and the transcription factor FoxP3. It has therefore recently been suggested that HTLV-1 selectively infects and transforms Tregs. We show that HTLV-1 induces and maintains a high frequency of FoxP3+ T cells by inducing expression of the chemokine CCL22; the frequency is especially high in patients with chronic ATLL. In turn, the FoxP3+ T cells exert both potentially beneficial and harmful effects: they suppress the growth of autologous ATLL clones and may also suppress the host's cytotoxic T lymphocyte response, which normally limits HTLV-1 replication and reduces the risk of HTLV-1-associated diseases. Although ATLL cells may exert immune suppressive effects, we conclude that ATLL is not necessarily a tumour of classical FoxP3+ Tregs.
人类 T 淋巴细胞白血病病毒 1 型（HTLV-1）可导致约 5%的 HTLV-1 感染者罹患成人 T 细胞白血病/淋巴瘤（ATLL）。ATLL 细胞常表达多种特征性调节性 T 细胞（Treg）的分子，尤其是 CD4、CD25 和转录因子 FoxP3。因此，最近有人提出 HTLV-1 选择性感染和转化 Treg。我们发现 HTLV-1 通过诱导趋化因子 CCL22 的表达，诱导 FoxP3+T 细胞的高频率产生，并维持其存活；在慢性 ATLL 患者中，该频率尤其高。反过来，FoxP3+T 细胞发挥潜在有益和有害的作用：它们抑制自体 ATLL 克隆的生长，也可能抑制宿主的细胞毒性 T 淋巴细胞反应，而后者通常限制 HTLV-1 的复制并降低 HTLV-1 相关疾病的风险。尽管 ATLL 细胞可能发挥免疫抑制作用，但我们的结论是，ATLL 不一定是经典 FoxP3+Treg 的肿瘤。
