CD80 and CD86 control antiviral CD8+ T-cell function and immune surveillance of murine gammaherpesvirus 68
CD80 and CD86 control antiviral CD8+ T-cell function and immune surveillance of murine gammaherpesvirus 68
复制标题
DOI：
10.1128/jvi.00422-06
复制
发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Usherwood, Edward J.
中科院分区：
文献类型：
--
作者：
Fuse, Shinichiro;Obar, Joshua J.;Usherwood, Edward J.
抗原提呈细胞上CD80和CD86与T细胞上CD28的相互作用是T细胞活化过程中重要的共刺激信号。虽然简单化的双信号假说近年来受到了不同共刺激物的挑战，但这一经典途径已被证明能显著影响抗病毒、体液和细胞免疫反应。CD80/CD86-CD28通路如何影响慢性或潜伏性感染的控制尚不清楚。在这项研究中，我们研究了它在对抗小鼠γ疱疹病毒68 （MHV-68）的抗病毒免疫应答和CD80/CD86（-/-）小鼠的免疫监测中的作用。在缺乏CD80/CD86的情况下，一级抗病毒CD8(+) t细胞反应和中和抗体的诱导严重受损。在长期的免疫监测中，病毒特异性CD8(+) T细胞在ifn - γ的产生和继发性扩增中受损，并表现出表型改变。令人惊讶的是，在肺中观察到低水平的病毒再激活，并且这种作用与CD28和CTLA-4无关。因此，CD80和CD86，通过CD28和可能的另一个未知受体发出信号，是对小鼠γ疱疹病毒的最佳免疫监视和抗病毒免疫反应所必需的。
The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86(-/-) mice. In the absence of CD80/CD86, primary antiviral CD8(+) T-cell responses and the induction of neutralizing antibodies were severely impaired. During long-term immune surveillance, the virus-specific CD8(+) T cells were impaired in IFN-gamma production and secondary expansion and exhibited an altered phenotype. Surprisingly, a low level of viral reactivation in the lung was observed, and this effect was independent of CD28 and CTLA-4. Thus, CD80 and CD86, signaling through CD28 and possibly another unidentified receptor, are required for optimal immune surveillance and antiviral immune responses to murine gammaherpesvirus.