Antibody-mediated control of persistent γ-herpesvirus infection
Antibody-mediated control of persistent γ-herpesvirus infection
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DOI：
10.4049/jimmunol.168.8.3958
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发表时间：
2002-04-15
影响因子：
4.4
通讯作者：
Blackman, MA
中科院分区：
文献类型：
--
作者：
Kim, IJ;Flaño, E;Blackman, MA
人类γ-疱疹病毒，EBV和卡波西肉瘤相关疱疹病毒，建立终身潜伏期，并可在免疫功能低下的个体中重新激活。T细胞在控制持续性EBV感染中发挥重要作用，而体液免疫的作用尚不清楚。鼠γ-疱疹病毒-68与人γ-疱疹病毒具有生物学和结构相似性，并为解剖免疫控制机制提供了重要的体内实验模型。在当前的研究中，使用CD 28（-/-）小鼠来解决Ab在控制持续性鼠γ-疱疹病毒-68感染中的作用。CD 28（-/-）小鼠肺部的莱特尔感染得到控制，B细胞的潜伏期维持在正常频率。虽然类转换的病毒特异性抗体最初产生的情况下，生发中心，滴度和病毒中和活性迅速减弱。具有受损Ab应答的CD 28（-/-）小鼠中的T细胞耗竭，而具有完整Ab应答的对照小鼠中的T细胞耗竭未导致脾和肺中的潜伏期的显著复发。免疫血清的被动转移可防止复发。这些数据直接证明了体液免疫对控制γ-疱疹病毒潜伏期的重要贡献，并对临床干预具有重要意义。
The human gamma-herpesviruses, EBV and Kaposi's sarcoma-associated herpesvirus, establish life-long latency and can reactivate in immunocompromised individuals. T cells play an important role in controlling persistent EBV infection, whereas a role for humoral immunity is less clear. The murine gamma-herpesvirus-68 has biological and structural similarities to the human gamma-herpesviruses, and provides an important in vivo experimental model for dissecting mechanisms of immune control. In the current studies, CD28(-/-) mice were used to address the role of Abs in control of persistent murine gamma-herpesvirus-68 infection. Lytle infection was controlled in the lungs of CD28(-/-) mice, and latency was maintained in B cells at normal frequencies. Although class-switched virus-specific Abs were initially generated in the absence of germinal centers, titers and viral neutralizing activity rapidly waned. T cell depletion in CD28(-/-) mice with compromised Ab responses, but not in control mice with intact Ab responses, resulted in significant recrudescence from latency, both in the spleen and the lung. Recrudescence could be prevented by passive transfer of immune serum. These data directly demonstrate an important contribution of humoral immunity to control of gamma-herpesvirus latency, and have significant implications for clinical intervention.