CD4+ T-lymphocyte-induced Epstein-Barr virus reactivation in a patient with severe hypersensitivity to Mosquito bites and Epstein-Barr virus-infected NK cell lymphocytosis
CD4+ T-lymphocyte-induced Epstein-Barr virus reactivation in a patient with severe hypersensitivity to Mosquito bites and Epstein-Barr virus-infected NK cell lymphocytosis
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DOI：
10.1001/archderm.139.12.1601
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发表时间：
2003-12-01
影响因子：
--
通讯作者：
Yoshikawa, K
中科院分区：
文献类型：
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作者：
Asada, H;Miyagawa, S;Yoshikawa, K
背景：与EB病毒(EBV)感染相关的自然杀伤(NK)细胞增多症通常对蚊子叮咬(HMB)表现出严重的超敏反应，其特征是局部皮肤反应强烈，全身症状如高热、淋巴结病和肝脾肿大。然而，HMB的诱导机制仍不清楚。观察：我们调查了一例典型的HMB伴EBV阳性NK细胞增多症。蚊虫叮咬部位以CD4(+)T细胞为主，EBV阳性细胞较少。蚊子唾液腺提取物对CD4(+)T细胞有反应，而对CD8(+)T细胞或NK细胞无反应。有趣的是，用蚊子提取物激活的NK细胞和CD4(+)T细胞共培养，可以诱导NK细胞表达EBV裂解周期蛋白。此外，病毒裂解循环反式激活剂BZLF1在蚊子提取物的抓痕试验中可在皮肤损伤处检测到表达。结论：CD4(+)T细胞在蚊虫叮咬引起的皮肤初始反应中起重要作用，并可能在NK细胞中EBV潜伏感染的重新激活中起关键作用。在我们的病例中，病毒的重新激活导致了传染性单核细胞增多症样全身性症状的发病。
Background: Natural killer (NK) cell lymphocytosis associated with Epstein-Barr virus (EBV) infection often shows severe hypersensitivity to mosquito bites (HMB) characterized by intense local skin reactions and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. However, the induction mechanism of HMB is still unclear.Observations: We investigated a typical case of HMB with EBV-positive NK cell lymphocytosis. CD4(+) T cells dominantly infiltrated the site of the mosquito bite, while EBV-positive cells were few in comparison. CD4(+) T cells, but not CD8(+) T cells or NK cells, responded to the mosquito salivary gland extracts. Interestingly, coculturing of the NK cells and CD4(+) T cells activated by mosquito extracts induced expression of EBV lytic-cycle proteins in the NK cells. Furthermore, the expression of BZLF1, a viral lytic-cycle transactivator, was detectable at the skin lesion induced by scratch patch testing with mosquito extract. The EBV DNA copy number levels in the plasma were elevated in systemic HMB symptoms compared with the normal condition.Conclusions: CD4(+) T cells are important for the primary skin reaction to mosquito bites and might play a key role in reactivation of latent EBV infection in NK cells. This viral reactivation contributed to the pathogenesis of the infectious mononucleosis-like systemic symptoms of HMB in our present case.