Reduction in the Number of Varicella-Zoster Virus-Specific T-Cells in Immunocompromised Children with Varicella
Reduction in the Number of Varicella-Zoster Virus-Specific T-Cells in Immunocompromised Children with Varicella
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DOI：
10.1620/tjem.250.181
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发表时间：
2020-03-01
影响因子：
2.2
通讯作者：
Ohga, Shouichi
中科院分区：
文献类型：
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作者：
Murata, Kenji;Hoshina, Takayuki;Ohga, Shouichi
水痘带状疱疹病毒（VZV）在免疫功能低下的宿主中引起危及生命的感染。健康受试者对VZV的免疫应答已被严格评估，但对免疫受损个体的免疫应答知之甚少。本研究旨在阐明免疫功能低下儿童对VZV感染的主要反应。这项前瞻性研究招募了6名接受类固醇或免疫抑制剂的免疫功能低下儿童（中位年龄33个月;范围20-62）和10名免疫功能正常的水痘儿童（中位年龄32个月;范围15-81）。免疫功能低下的儿童是三名急性淋巴细胞白血病患者，两名肝移植受者和一名幼年特发性关节炎患者。在急性期或恢复期研究了VZV刺激产生的产生干扰素γ的CD 69（+）T细胞（VZV特异性T细胞）。为了进一步说明免疫抑制剂的直接作用，我们分析了VZV特异性T细胞的数量后刺激外周血单核细胞从健康成人与减毒活VZV与或不与泼尼松龙，环孢素A，或他克莫司。免疫功能低下儿童恢复期淋巴细胞循环数低于免疫功能正常儿童，而急性期淋巴细胞循环数无明显差异。在急性期，免疫功能低下的患者表现出较低的VZV特异性CDWT细胞计数比免疫功能正常的受试者。相反，在恢复期，免疫功能低下的患者VZV特异性CD 4（+）T细胞计数低于免疫功能正常的宿主。在体外培养的活化淋巴细胞与泼尼松龙或免疫抑制剂显着降低VZV特异性CD 8（+）T细胞的比例。总之，急性期VZV特异性CD 8（+）T细胞和恢复期VZV特异性CD 4（+）T细胞数量的减少可能是免疫功能低下儿童严重水痘的原因。
Varicella zoster virus (VZV) causes a life-threatening infection in immunocompromised hosts. The immune response to VZV of healthy subjects has been rigorously assessed, but little is known about that of immunocompromised individuals. This study aimed to clarify the primary response to VZV infection in immunocompromised children. This prospective study enrolled six immunocompromised children (median age, 33 months; range, 20-62) receiving steroids or immunosuppressants, and 10 immunocompetent children (median age, 32 months; range, 15-81) with varicella. The immunocompromised children were three patients with acute lymphoblastic leukemia, two recipients with liver transplantation and one patient with juvenile idiopathic arthritis. Interferon-gamma-producing CD69(+)T-cells produced by VZV stimulation (VZV-specific T-cells) were studied during the acute or convalescent phase. To further address the direct effect of immunosuppressants, we analyzed the number of VZV-specific T-cells after stimulating peripheral blood mononuclear cells obtained from healthy adults with live-attenuated VZV with or without prednisolone, cyclosporine-A, or tacrolimus. The circulating numbers of lymphocytes in the convalescent stage but not acute stage were lower in immunocompromised children compared with immunocompetent children. In the acute stage, immunocompromised patients showed lower VZV-specific CDWT-cell counts than immunocompetent subjects. In contrast, in the convalescent phase, immunocompromised patients had lower VZV-specific CD4(+)T-cell counts than immunocompetent hosts. The in vitro culture of activated lymphocytes with prednisolone or immunosuppressants significantly decreased the proportion of VZV-specific CD8(+)T-cells. In conclusion, the decreased numbers of VZV-specific CD8(+)T-cells during the acute phase and VZV-specific CD4(+)T-cells during the convalescent phase of disease may account for severe varicella in immunocompromised children.