Department of Immunology, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Signalling Research Centres Centre for Biological Signalling Studies (BIOSS) and Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany.
Front Immunol. 2022 Aug 11;13:920888. doi: 10.3389/fimmu.2022.920888. eCollection 2022.
The human T-cell leukemia virus type 1 (HTLV-1) is the cause of serious malignant and inflammatory diseases, including adult T-cell leukemia and lymphoma and tropical spastic paraparesis. The potential protective role of γδ T cells in HTLV-1 infection remains unclear. Here, demonstrate that there is a decrease in the amount of Vγ9Vδ2 T cells in patients with HTLV-1, especially in those with HTLV-1 associated pathologies. This suggests that γδ T cells could be involved in controlling the virus. Indeed, we found that Vγ9Vδ2 T cells, expanded from non-infected individuals, can kill cells expressing the viral proteins HBZ and Tax and this phenotype is reversed in the presence of mevastatin. Cytotoxicity by Vγ9Vδ2 T cells was not associated with an increase of INF-γ production. In sharp contrast, killing by NK cells was reduced by Tax expression. Thus, our study provides initial evidence for a potential protective role of Vγ9Vδ2 T cells against HTLV-1 infection. Therapeutic exploitation of these insights is feasible with current technologies of T-cell therapies and could provide novel tools to prevent and treat HTLV-1-associated malignancies and neurologic complications.
人类 T 细胞白血病病毒 1 型（HTLV-1）是引起严重恶性和炎症性疾病的原因，包括成人 T 细胞白血病和淋巴瘤以及热带痉挛性截瘫。γδ T 细胞在 HTLV-1 感染中的潜在保护作用尚不清楚。在这里，我们证明 HTLV-1 患者体内 Vγ9Vδ2 T 细胞数量减少，尤其是那些患有 HTLV-1 相关疾病的患者。这表明 γδ T 细胞可能参与控制病毒。事实上，我们发现从未感染个体中扩增的 Vγ9Vδ2 T 细胞可以杀死表达病毒蛋白 HBZ 和 Tax 的细胞，而在加入甲羟戊酸时，这种表型会逆转。Vγ9Vδ2 T 细胞的细胞毒性与 INF-γ 产生的增加无关。相比之下，Tax 表达会降低 NK 细胞的杀伤能力。因此，我们的研究为 Vγ9Vδ2 T 细胞对 HTLV-1 感染的潜在保护作用提供了初步证据。利用当前的 T 细胞治疗技术，对这些见解进行治疗性利用是可行的，并且可以为预防和治疗 HTLV-1 相关恶性肿瘤和神经并发症提供新的工具。
