Altered levels of memory T cell subsets and common γc cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment

BackgroundCD4+ and CD8+ T cells are central players in immunity to helminth infections. However, the role of T cell subsets in human helminth infections is not well understood. In addition, the common γc cytokines, IL-2, IL-4, IL-7, IL-9 and IL-15 play an important role in the maintenance of these CD4+ and CD8+ T cell subsets.MethodsTo examine the major T cell subsets and their association with the common γc cytokines, the absolute numbers of CD4+ and CD8+ naïve, central memory, effector memory and effector cells and the plasma levels of IL-2, IL-4, IL-7, IL-9 and IL-15 were measured in Strongyloides stercoralis (Ss) infected (INF, n = 60), helminth—uninfected (UN, n = 58) and in post treatment INF individuals.ResultsSs infection is characterized by significantly increased absolute numbers of naïve and decreased absolute numbers of central and effector memory CD4+ T cells in comparison to UN individuals. No significant difference in the numbers of CD8+ T cell subsets was observed between the groups. The numbers of naïve cells and central memory CD4+ T cells were significantly reversed after anthelmintic treatment. Circulating levels of IL-2, IL-7 and IL-15 were significantly diminished, whereas the levels of IL-4 and IL-9 were significantly increased in INF compared to UN individuals. Following anthelminthic treatment, IL-2, IL-7 and IL-15 levels were significantly increased, while IL-4 and IL-9 levels were significantly decreased. Our data also showed a significant positive correlation between the levels of IL-7 and the numbers of central and effector memory CD4+ T cells.ConclusionSs infection is characterized by alterations in the absolute numbers of CD4+ T cell subsets and altered levels of common γc cytokines IL-2, IL-4, IL-7, IL-9 and IL-15; alterations which are partially reversed after anthelmintic treatment.背景：CD4+与CD8+ T细胞是抗蠕虫感染免疫的核心效应细胞，但目前T细胞亚群在人类蠕虫感染中的作用尚未完全明确。此外，常见γc细胞因子（common γc cytokines）IL-2、IL-4、IL-7、IL-9及IL-15在维持上述CD4+与CD8+ T细胞亚群稳态中发挥关键作用。方法：为探究主要T细胞亚群及其与常见γc细胞因子的关联，本研究在粪类圆线虫（Strongyloides stercoralis, Ss）感染者（感染组，INF，n=60）、蠕虫未感染者（未感染组，UN，n=58）以及驱虫治疗后的感染者中，检测了CD4+和CD8+初始、中央记忆、效应记忆及效应T细胞的绝对计数，同时测定了IL-2、IL-4、IL-7、IL-9及IL-15的血浆水平。结果：与未感染组相比，粪类圆线虫感染以初始CD4+ T细胞绝对计数升高、中央记忆与效应记忆CD4+ T细胞绝对计数显著降低为特征。各组间CD8+ T细胞亚群的绝对计数无显著差异。驱虫治疗后，初始CD4+ T细胞与中央记忆CD4+ T细胞的数量显著恢复。与未感染组相比，感染组血浆IL-2、IL-7及IL-15水平显著降低，而IL-4与IL-9水平显著升高。驱虫治疗后，IL-2、IL-7及IL-15水平显著升高，IL-4与IL-9水平则显著降低。本研究数据还显示，IL-7水平与中央记忆及效应记忆CD4+ T细胞数量呈显著正相关。结论：粪类圆线虫感染以CD4+ T细胞亚群绝对计数改变及常见γc细胞因子IL-2、IL-4、IL-7、IL-9和IL-15水平异常为特征，上述异常在驱虫治疗后可得到部分逆转。