Institute for Immunology, Ludwig-Maximilians-University Munich Munich, Germany.
Front Immunol. 2012 Nov 26;3:348. doi: 10.3389/fimmu.2012.00348. eCollection 2012.
DCs very potently activate CD8(+) T cells specific for viral peptides bound to MHC class I molecules. However, many viruses have evolved immune evasion mechanisms, which inactivate infected DCs and might reduce priming of T cells. Then MHC class I cross-presentation of exogenous viral Ag by non-infected DCs may become crucial to assure CD8(+) T cell responses. Although many vital functions of infected DCs are inhibited in vitro by many different viruses, the contributions of cross-presentation to T cell immunity when confronted with viral immune inactivation in vivo has not been demonstrated up to now, and remains controversial. Here we show that priming of Herpes Simplex Virus (HSV)-, but not murine cytomegalovirus (mCMV)-specific CD8(+) T cells was severely reduced in mice with a DC-specific cross-presentation deficiency. In contrast, while CD8(+) T cell responses to mutant HSV, which lacks crucial inhibitory genes, also depended on CD8α(+) DCs, they were independent of cross-presentation. Therefore HSV-specific CTL-responses entirely depend on the CD8α(+) DC subset, which present via direct or cross-presentation mechanisms depending on the immune evasion equipment of virus. Our data establish the contribution of cross-presentation to counteract viral immune evasion mechanisms in some, but not all viruses.
树突状细胞（DCs）能够非常有效地激活针对 MHC I 类分子结合的病毒肽的 CD8(+) T 细胞。然而，许多病毒已经进化出免疫逃避机制，这些机制会使感染的 DCs失活，并可能减少 T 细胞的激活。然后，非感染的 DC 对异源病毒 Ag 的 MHC I 类交叉呈递可能对于保证 CD8(+) T 细胞反应变得至关重要。尽管许多不同的病毒在体外抑制了感染的 DC 的许多重要功能，但迄今为止，在体内面对病毒免疫失活时，交叉呈递对 T 细胞免疫的贡献尚未得到证明，并且仍然存在争议。在这里，我们显示，在具有 DC 特异性交叉呈递缺陷的小鼠中，单纯疱疹病毒（HSV）-，但不是鼠巨细胞病毒（mCMV）-特异性 CD8(+) T 细胞的启动严重减少。相比之下，虽然缺乏关键抑制基因的突变 HSV 也依赖于 CD8α(+) DC 来产生 CD8(+) T 细胞反应，但它们不依赖于交叉呈递。因此，HSV 特异性 CTL 反应完全依赖于 CD8α(+) DC 亚群，该亚群通过直接或交叉呈递机制取决于病毒的免疫逃避装备。我们的数据确立了交叉呈递对某些但不是所有病毒的免疫逃避机制的贡献。
