Laboratório de Imunologia Básica e Aplicada, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
J Leukoc Biol. 2019 Sep;106(3):607-618. doi: 10.1002/JLB.MA1118-467R. Epub 2019 Jul 9.
Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic inflammatory disease that leads to gradual loss of motor movement as a result of the death of spinal cord cells through immune mediated mechanisms. The risk to develop HAM/TSP disease positively correlates with the magnitude of HTLV-1 proviral load. Gamma-delta T lymphocytes have been recognized as important players in a variety of infectious diseases. Therefore, we have investigated interactions between HTLV-1 infection and γδ T lymphocytes during HAM/TSP. Similar frequencies of total γδ T lymphocytes and their Vγ9δ2 and Vγ9δ2 subpopulations were observed in HAM/TSP patients. However, T lymphocytes obtained from HTLV-1 carriers displayed significantly higher rates of spontaneous proliferation and NKp30 expression when compared to cells from uninfected donors. In addition, an important decrease in the frequency of granzyme B γδ T lymphocytes (approximately 50%) was observed in HAM/TSP patients. Higher proportion of IFN-γ γδ T lymphocytes was found in HTLV-1-infected patients, which positively correlated with the HTLV-1 proviral load in peripheral blood mononuclear cells. Collectively, our data indicates that HTLV-1 infection leads to phenotypic and functional changes in the population of γδ T lymphocyte population, suggesting that HTLV-1 infection modulates functions associated to these cells, which might be involved in controlling the infection or in the development of HTLV-1-associated diseases.
人类 T 细胞嗜淋巴细胞病毒 1 型（HTLV-1）是 HTLV-1 相关脊髓病/热带痉挛性截瘫（HAM/TSP）的病原体，这是一种慢性炎症性疾病，通过免疫介导机制导致脊髓细胞死亡，从而导致运动功能逐渐丧失。发生 HAM/TSP 疾病的风险与 HTLV-1 前病毒载量的大小呈正相关。γδ T 淋巴细胞已被认为是多种传染病的重要参与者。因此，我们研究了 HAM/TSP 期间 HTLV-1 感染和γδ T 淋巴细胞之间的相互作用。在 HAM/TSP 患者中观察到总γδ T 淋巴细胞及其 Vγ9δ2 和 Vγ9δ2 亚群的频率相似。然而，与未感染供体的细胞相比，从 HTLV-1 携带者中获得的 T 淋巴细胞显示出明显更高的自发增殖率和 NKp30 表达率。此外，在 HAM/TSP 患者中还观察到颗粒酶 B γδ T 淋巴细胞（约 50%）的频率显著降低。在 HTLV-1 感染的患者中发现 IFN-γ γδ T 淋巴细胞的比例较高，与外周血单个核细胞中的 HTLV-1 前病毒载量呈正相关。总之，我们的数据表明，HTLV-1 感染导致 γδ T 淋巴细胞群体的表型和功能发生变化，表明 HTLV-1 感染调节与这些细胞相关的功能，这可能与控制感染或 HTLV-1 相关疾病的发展有关。
