Kim In-Jeong, Flaño Emilio, Woodland David L, Blackman Marcia A
Trudeau Institute, Saranac Lake, NY 12983, USA.
J Immunol. 2002 Apr 15;168(8):3958-64. doi: 10.4049/jimmunol.168.8.3958.
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. Lytic 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.
人类γ-疱疹病毒，即EB病毒和卡波西肉瘤相关疱疹病毒，会建立终身潜伏感染，并且在免疫功能低下的个体中可能重新激活。T细胞在控制持续性EB病毒感染中发挥重要作用，而体液免疫的作用尚不清楚。小鼠γ-疱疹病毒68与人类γ-疱疹病毒在生物学和结构上具有相似性，为剖析免疫控制机制提供了重要的体内实验模型。在当前研究中，使用CD28基因敲除小鼠来探讨抗体在控制持续性小鼠γ-疱疹病毒68感染中的作用。在CD28基因敲除小鼠的肺部，裂解感染得到控制，并且B细胞中潜伏期以正常频率维持。尽管最初在没有生发中心的情况下产生了类别转换的病毒特异性抗体，但抗体滴度和病毒中和活性迅速下降。抗体反应受损的CD28基因敲除小鼠中的T细胞耗竭，而非抗体反应完整的对照小鼠中的T细胞耗竭，导致脾脏和肺部潜伏感染显著复发。通过被动转移免疫血清可预防复发。这些数据直接证明了体液免疫对控制γ-疱疹病毒潜伏感染的重要贡献，并且对临床干预具有重要意义。
