Phenotypic Characterization of Peripheral T Cells and Their Dynamics in Scrub Typhus Patients

BackgroundScrub typhus, caused by Orientia tsutsugamushi infection, is one of the main causes of febrile illness in the Asia-Pacific region. Although cell-mediated immunity plays an important role in protection, little is known about the phenotypic changes and dynamics of leukocytes in scrub typhus patients. Methodology/Principal FindingsTo reveal the underlying mechanisms of immunological pathogenesis, we extensively analyzed peripheral blood leukocytes, especially T cells, during acute and convalescent phases of infection in human patients and compared with healthy volunteers. We observed neutrophilia and CD4+ T lymphopenia in the acute phase of infection, followed by proliferation of CD8+ T cells during the convalescent phase. Massive T cell apoptosis was detected in the acute phase and preferential increase of CD8+ T cells with activated phenotypes was observed in both acute and convalescent phases, which might be associated or correlated with elevated serum IL-7 and IL-15. Interestingly, peripheral Treg cells were significantly down-regulated throughout the disease course. Conclusions/SignificanceThe remarkable decrease of CD4+ T cells, including Treg cells, during the acute phase of infection may contribute to the loss of immunological memory that are often observed in vaccine studies and recurrent human infection.【背景】恙虫病（Scrub typhus）由恙虫病东方体（Orientia tsutsugamushi）感染引发，是亚太地区发热性疾病的主要致病原因之一。尽管细胞介导免疫在抗感染防护中发挥关键作用，但目前对恙虫病患者体内白细胞的表型变化与动态特征仍知之甚少。 【研究方法与主要结果】为阐明该病免疫发病的潜在机制，本研究对人类患者感染急性期与恢复期的外周血白细胞（尤其是T细胞）进行了全面分析，并与健康志愿者进行对照。研究观察到，感染急性期患者出现中性粒细胞增多与CD4+ T淋巴细胞减少，恢复期则伴随CD8+ T细胞的增殖；急性期可检测到大量T细胞凋亡，且在急性期与恢复期均观察到具有活化表型的CD8+ T细胞优先扩增，这一现象可能与血清IL-7、IL-15水平升高相关。值得注意的是，外周血调节性T细胞（Treg cells）在整个病程中均显著下调。 【结论与意义】感染急性期CD4+ T细胞（包括调节性T细胞）的显著减少，可能导致免疫记忆的丧失，而这一表现在疫苗研究与复发性人类感染中常被观察到。