Medical Parasitology and Mycology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
PLoS Negl Trop Dis. 2010 Oct 12;4(10):e845. doi: 10.1371/journal.pntd.0000845.
In human leishmaniasis Th1/Th2 dichotomy similar to murine model is not clearly defined and surrogate marker(s) of protection is not yet known. In this study, Th1/Th2 cytokines (IL-5, IL-10, IL-13 and IFN-γ) profile induced by purified CD4(+)/CD8(+) T cells in response to Leishmania antigens were assessed at transcript and protein levels in 14 volunteers with a history of self-healing cutaneous leishmaniasis (HCL) and compared with 18 healthy control volunteers.
METHODOLOGY/PRINCIPAL FINDINGS: CD4(+)/CD8(+)/CD14(+) cells were purified from peripheral blood using magnetic beads; CD4(+)/CD8(+) T cells were co-cultured with autologous CD14(+) monocytes in the presence of soluble Leishmania antigens (SLA). Stimulation of either CD4(+) T cells or CD8(+) T cells of HCL volunteers with SLA induced a significantly (P<0.05) higher IFN-γ production compared with the cells of controls. Upregulation of IFN-γ gene expression in CD4(+) cells (P<0.001) and CD8(+) cells (P = 0.006) of HCL volunteers was significantly more than that of controls. Significantly (P<0.05) higher fold-expression of IFN-γ gene was seen in CD4(+) cells than in CD8(+) cells. In HCL volunteers a significantly (P = 0.014) higher number of CD4(+) cells were positive for intracellular IFN-γ production than CD8(+) cells.
CONCLUSIONS/SIGNIFICANCE: Collectively, the volunteers have shown maintenance of specific long-term immune responses characterized by a strong reaction to leishmanin skin test and IFN-γ production. The dominant IFN-γ response was the result of expansion of both CD4(+) and CD8(+) T cells. The results suggested that immune response in protected individuals with a history of zoonotic cutaneous leishmaniasis (ZCL) due to L. major is mediated not only through the expansion of antigen-specific IFN-γ producing CD4(+) Th1 cells, but also through IFN-γ producing CD8(+) T cells.
在人类利什曼病中，类似于鼠类模型的 Th1/Th2 二分法尚不清楚，也尚未确定保护的替代标志物。在这项研究中，我们评估了 14 名有自我治愈皮肤利什曼病（HCL）病史的志愿者和 18 名健康对照志愿者对利什曼抗原产生的纯化 CD4+/CD8+T 细胞诱导的 Th1/Th2 细胞因子（IL-5、IL-10、IL-13 和 IFN-γ）的转录和蛋白水平。
方法/主要发现：使用磁性珠从外周血中纯化 CD4+/CD8+/CD14+细胞；将 CD4+/CD8+T 细胞与自体 CD14+单核细胞在可溶性利什曼抗原（SLA）存在下共培养。与对照组相比，HCL 志愿者的 SLA 刺激 CD4+T 细胞或 CD8+T 细胞诱导 IFN-γ 产生明显升高（P<0.05）。HCL 志愿者 CD4+细胞（P<0.001）和 CD8+细胞（P=0.006）中 IFN-γ 基因表达的上调明显高于对照组。与 CD8+细胞相比，CD4+细胞中 IFN-γ 基因的表达倍数明显升高（P<0.05）。在 HCL 志愿者中，与 CD8+细胞相比，CD4+细胞中 IFN-γ 产生的阳性细胞数量明显更多（P=0.014）。
结论/意义：总之，志愿者表现出维持特定的长期免疫反应，其特征为对利什曼菌素皮肤试验和 IFN-γ 产生的强烈反应。主导的 IFN-γ 反应是 CD4+和 CD8+T 细胞扩张的结果。结果表明，在有动物源性皮肤利什曼病（ZCL）病史的个体中，由于 L. major 引起的免疫反应不仅通过扩张抗原特异性 IFN-γ 产生的 CD4+Th1 细胞来介导，而且还通过 IFN-γ 产生的 CD8+T 细胞来介导。
