Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
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DOI：
10.1093/infdis/jiy493
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发表时间：
2019-01-07
期刊：
影响因子：
--
通讯作者：
Harper L
中科院分区：
文献类型：
--
作者：
Chanouzas D;Sagmeister M;Faustini S;Nightingale P;Richter A;Ferro CJ;Morgan MD;Moss P;Harper L
感染是抗神经细胞胞质抗体相关性血管炎的主要死亡原因。在这里，我们表明，抑制亚临床再活化的巨细胞病毒限制CD4+CD28null T细胞的扩增，这是与改善免疫反应的T细胞依赖性肺炎球菌疫苗的挑战。感染是抗神经细胞胞质抗体相关性血管炎（AAV）的主要死亡原因。CD4+CD28null T细胞的扩增与感染和死亡风险增加相关，但仅存在于巨细胞病毒（CMV）血清阳性个体中。我们假设亚临床CMV再激活驱动CD4+ CD28无效T细胞扩增，这与对异源抗原的免疫应答受损有关，抗病毒治疗可能会改善这种情况。在一项概念验证的开放标签临床试验中，38名CMV血清阳性AAV患者随机接受伐昔洛韦治疗6个月或不进行干预。每月测量血浆和尿液中的CMV再活化。在基线和6个月时计数CD4+CD28null T细胞。6个月时，36名患者接种了13价肺炎球菌疫苗。在接种前和接种后4周测定血清型特异性免疫球蛋白G，以计算抗体应答率。伐昔洛韦治疗抑制亚临床CMV再活化，降低CD4+ CD28无效T细胞比例。CD4+CD28null T细胞减少与疫苗应答改善相关，而CMV再活化与疫苗接种应答降低相关。此外，CD4+CD28null T细胞的扩增与CD4区室功能能力的降低相关。CMV的抑制可以改善AAV患者对T细胞依赖性肺炎球菌疫苗接种的免疫应答，从而提供潜在的临床益处。NCT01633476。
Infection is a leading cause of death in antineutrophil cytoplasmic antibody–associated vasculitis. Here we show that suppression of subclinical reactivation of cytomegalovirus limits CD4+CD28null T-cell expansion and that this is associated with improved immune response to a T-cell–dependent pneumococcal vaccine challenge. Infection is the leading cause of death in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Expansion of CD4+CD28null T cells is associated with increased risk of infection and mortality, but is only present in cytomegalovirus (CMV)–seropositive individuals. We hypothesized that subclinical CMV reactivation drives CD4+CD28null T-cell expansion, that this is associated with impaired immune response to heterologous antigens, and that antiviral therapy may ameliorate this. In a proof-of-concept open-label clinical trial, 38 CMV-seropositive AAV patients were randomized to receive valacyclovir for 6 months or no intervention. CMV reactivation was measured monthly in plasma and urine. CD4+CD28null T cells were enumerated at baseline and at 6 months. At 6 months, 36 patients were vaccinated with a 13-valent pneumococcal vaccine. Serotype-specific immunoglobulin G was assayed before and 4 weeks postvaccination to calculate the antibody response ratio. Valacyclovir treatment suppressed subclinical CMV reactivation and reduced CD4+CD28null T-cell proportion. CD4+CD28null T-cell reduction correlated with improved vaccine response, whereas CMV reactivation associated with reduced response to vaccination. Furthermore, expansion of CD4+CD28null T cells was associated with a reduction in the functional capacity of the CD4 compartment. Suppression of CMV may improve the immune response to a T-cell–dependent pneumococcal vaccination in patients with AAV, thus offering potential clinical benefit. NCT01633476.
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