Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
J Immunol. 2012 Apr 1;188(7):3071-9. doi: 10.4049/jimmunol.1103554. Epub 2012 Mar 5.
We recently identified a protective MHC class Ib-restricted CD8 T cell response to infection with mouse polyomavirus. These CD8 T cells recognize a peptide from aa 139-147 of the VP2 viral capsid protein bound to the nonpolymorphic H-2Q9 molecule, a member of the Qa-2 family of β(2)m-associated MHC class Ib molecules. Q9:VP2.139-specific CD8 T cells exhibit an unusual inflationary response characterized by a gradual expansion over 3 mo followed by a stable maintenance phase. We previously demonstrated that Q9:VP2.139-specific CD8 T cells are dependent on Ag for expansion, but not for long-term maintenance. In this study, we tested the hypothesis that the expansion and maintenance components of the Q9:VP2.139-specific T cell response are differentially dependent on CD4 T cell help and CD28 costimulation. Depletion of CD4(+) cells and CD28/CD40L blockade impaired expansion of Q9:VP2.139-specific CD8 T cells, and intrinsic CD28 signaling was sufficient for expansion. In contrast, CD4 T cell insufficiency, but not CD28/CD40L blockade, resulted in a decline in frequency of Q9:VP2.139-specific CD8 T cells during the maintenance phase. These results indicate that the Q9:VP2.139-specific CD8 T cell response to mouse polyomavirus infection depends on CD4 T cell help and CD28 costimulation for inflationary expansion, but only on CD4 T cell help for maintenance.
我们最近发现了针对小鼠多瘤病毒感染的保护性 MHC 类 Ib 限制性 CD8 T 细胞反应。这些 CD8 T 细胞识别与非多态性 H-2Q9 分子（β(2)m 相关 MHC 类 Ib 分子的 Qa-2 家族的一员）结合的 VP2 病毒衣壳蛋白的 aa139-147 肽段。Q9:VP2.139 特异性 CD8 T 细胞表现出一种异常的膨胀反应，其特征为在 3 个月内逐渐扩张，然后进入稳定的维持阶段。我们之前证明，Q9:VP2.139 特异性 CD8 T 细胞依赖 Ag 进行扩张，但不依赖于长期维持。在这项研究中，我们检验了以下假说，即 Q9:VP2.139 特异性 T 细胞反应的扩张和维持成分在不同程度上依赖于 CD4 T 细胞辅助和 CD28 共刺激。CD4(+)细胞和 CD28/CD40L 阻断耗竭会损害 Q9:VP2.139 特异性 CD8 T 细胞的扩张，而内在的 CD28 信号足以促进扩张。相反，CD4 T 细胞不足，而不是 CD28/CD40L 阻断，导致 Q9:VP2.139 特异性 CD8 T 细胞在维持阶段的频率下降。这些结果表明，针对小鼠多瘤病毒感染的 Q9:VP2.139 特异性 CD8 T 细胞反应依赖于 CD4 T 细胞辅助和 CD28 共刺激来进行膨胀性扩张，但仅依赖于 CD4 T 细胞辅助来维持。
