Institute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Department of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Am J Trop Med Hyg. 2018 Mar;98(3):875-882. doi: 10.4269/ajtmh.16-0747. Epub 2017 Dec 21.
Manifestations of infection range from asymptomatic to symptomatic visceral leishmaniasis (VL). People with symptomatic VL (sVL) have suppressed immune responses against Leishmania antigens that are reversed after clinical cure. The intradermal leishmanin skin test (LST) is negative during sVL, but it becomes positive after treatment. The aim of this study was to compare T cell responses in individuals with sVL, recovered VL (RecVL), and endemic controls. Endemic controls were household contacts of a VL case and they were grouped by their LST results, either positive (LST+) or negative (LST-). Mononuclear cells were studied ex vivo or after stimulation with soluble Leishmania antigens (SLA); cell surface markers and cytokines were determined. T cells, ex vivo, from individuals with sVL and from LST+ individuals presented a higher activation for CD4 and CD8 cells expressing CD69. However, lymphocytes from sVL stimulated with SLA had lower percentages of CD4 and CD8 cells expressing CD69 and CD8 cells expressing CD25, with no release of interferon-γ or tumor necrosis factor. sVL subjects had lower percentage of memory cells (CD4 CD45RO+), ex vivo, without SLA stimulation than RecVL, LST+, or LST- ( = 0.0022). However, individuals with sVL had fewer regulatory cells after SLA stimulation (CD4 CD25, = 0.04 and CD4 FOXP3+, = 0.02) than RecVL. The decrease in specific memory and activated CD4 and CD8 cells, as in response to Leishmania antigens, could explain, in part, the immune impairment during sVL. Finally, protective T cell responses are long lasting because both RecVL or LST+ individuals maintain a specific protective response to Leishmania years after the primary infection.
感染的表现形式从无症状到有症状内脏利什曼病（VL）不等。有症状 VL（sVL）患者对利什曼原虫抗原的免疫反应受到抑制，在临床治愈后得到逆转。在 sVL 期间，皮内利什曼素皮肤试验（LST）呈阴性，但在治疗后呈阳性。本研究旨在比较 sVL、恢复 VL（RecVL）和地方性对照个体的 T 细胞反应。地方性对照是 VL 病例的家庭接触者，根据他们的 LST 结果分组，阳性（LST+）或阴性（LST-）。单核细胞在体外或用可溶性利什曼抗原（SLA）刺激后进行研究；测定细胞表面标志物和细胞因子。sVL 和 LST+个体的 T 细胞，在体外，表达 CD69 的 CD4 和 CD8 细胞的激活更高。然而，来自 sVL 的淋巴细胞用 SLA 刺激后，表达 CD69 和 CD25 的 CD4 和 CD8 细胞的百分比较低，没有释放干扰素-γ或肿瘤坏死因子。与 RecVL、LST+或 LST-相比，sVL 患者在没有 SLA 刺激时，记忆细胞（CD4 CD45RO+）的比例较低（ = 0.0022）。然而，与 RecVL 相比，sVL 患者在 SLA 刺激后，调节性细胞（CD4 CD25， = 0.04 和 CD4 FOXP3+， = 0.02）较少。针对利什曼抗原，特异性记忆和激活的 CD4 和 CD8 细胞的减少，可能部分解释了 sVL 期间的免疫损伤。最后，保护性 T 细胞反应是持久的，因为 RecVL 或 LST+个体在原发性感染多年后仍保持对利什曼的特异性保护性反应。
