Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Praadesh, India.
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
J Infect Dis. 2019 Jun 5;220(1):163-173. doi: 10.1093/infdis/jiz074.
Control of visceral leishmaniasis (VL) caused by Leishmania donovani requires interferon-γ production by CD4+ T cells. In VL patients, antiparasitic CD4+ T-cell responses are ineffective for unknown reasons. In this study, we measured the expression of genes associated with various immune functions in these cells from VL patients and compared them to CD4+ T cells from the same patients after drug treatment and from endemic controls. We found reduced GATA3, RORC, and FOXP3 gene expression in CD4+ T cells of VL patients, associated with reduced Th2, Th17, and FOXP3+CD4+ T regulatory cell frequencies in VL patient blood. Interleukin 2 (IL-2) was an important upstream regulator of CD4+ T cells from VL patients, and functional studies demonstrated the therapeutic potential of IL-2 for improving antiparasitic immunity. Together, these results provide new insights into the characteristics of CD4+ T cells from VL patients that can be used to improve antiparasitic immune responses.
内脏利什曼病（VL）由杜氏利什曼原虫引起，需要 CD4+T 细胞产生干扰素-γ。VL 患者对抗寄生虫的 CD4+T 细胞反应无效，原因不明。在这项研究中，我们测量了来自 VL 患者的这些细胞中与各种免疫功能相关的基因的表达，并将其与药物治疗后的同一患者的 CD4+T 细胞和来自地方性疾病对照者的 CD4+T 细胞进行了比较。我们发现 VL 患者的 CD4+T 细胞中 GATA3、RORC 和 FOXP3 基因表达降低，与 VL 患者血液中 Th2、Th17 和 FOXP3+CD4+T 调节性细胞频率降低有关。白细胞介素 2（IL-2）是 VL 患者 CD4+T 细胞的重要上游调节剂，功能研究表明 IL-2 具有改善抗寄生虫免疫的治疗潜力。总之，这些结果为 VL 患者 CD4+T 细胞的特征提供了新的见解，可用于改善抗寄生虫免疫反应。
