Trudeau Institute, Saranac Lake, NY 12983, USA.
J Immunol. 2011 Dec 15;187(12):6180-4. doi: 10.4049/jimmunol.1102745. Epub 2011 Nov 11.
CD4 T cells are essential for immune control of γ-herpesvirus latency. We previously identified a murine MHC class II-restricted epitope in γ-herpesvirus-68 gp150 (gp150(67-83)I-A(b)) that elicits CD4 T cells that are maintained throughout long-term infection. However, it is unknown whether naive cells can be recruited into the antiviral CD4 T cell pool during latency. In this study, we generate a mouse transgenic for a gp150-specific TCR and show epitope-specific activation of transgenic CD4 T cells during acute and latent infections. Furthermore, although only dendritic cells can stimulate virus-specific CD8 T cells during latency, we show that both dendritic cells and B cells stimulate transgenic CD4 T cells. These studies demonstrate that naive CD4 T cells specific for a viral glycoprotein can be stimulated throughout infection, even during quiescent latency, suggesting that CD4 T cell memory is maintained in part by the continual recruitment of naive cells.
CD4 T 细胞对于控制γ疱疹病毒潜伏至关重要。我们之前在γ疱疹病毒-68 的 gp150 中鉴定了一个受 MHC Ⅱ类限制的小鼠表位（gp150(67-83)I-A(b)），它能引发 CD4 T 细胞的应答，并且在长期感染中得到维持。然而，目前尚不清楚在潜伏感染期间，幼稚细胞是否能被招募到抗病毒的 CD4 T 细胞池。在这项研究中，我们构建了一种表达 gp150 特异性 TCR 的转基因小鼠，并在急性和潜伏感染期间观察到了该转基因 CD4 T 细胞的表位特异性激活。此外，尽管只有树突状细胞（dendritic cells，DCs）可以在潜伏感染期间刺激病毒特异性 CD8 T 细胞，但我们发现 DCs 和 B 细胞都可以刺激转基因 CD4 T 细胞。这些研究表明，针对病毒糖蛋白的幼稚 CD4 T 细胞可以在整个感染过程中被激活，即使在静止的潜伏感染期也是如此，这表明 CD4 T 细胞记忆的维持部分是通过幼稚细胞的持续招募实现的。
