Institute for Immunology, Ludwig-Maximilians-University, Munich, Germany.
Eur J Immunol. 2010 Apr;40(4):966-75. doi: 10.1002/eji.200939485.
To develop cytolytic effector functions, CD8(+) T lymphocytes need to recognize specific Ag/MHC class I complexes in the context of costimuli on Ag-presenting DC. Thereafter they differentiate into effector and memory CTL able to confer protection against pathogen infection. Using transgenic mice with DC-selective MHC class I expression and DC-specific versus ubiquitous vaccination regimen, we found that DC are sufficient to prime CTL responses. However, Ag recognition on parenchymal non-professional APC negatively affected CD8(+) T-cell responses in mice by inducing expression of the pro-apoptotic bcl2-family member bim in CTL. This unexpected induction of apoptosis in the early phase of effector CTL accumulation lead to suboptimal clonal burst size and diminished long-term memory. Thus, our data demonstrate that effector CTL differentiation and apoptosis are regulated independently. Moreover, Ag distribution on cells other than DC critically reduces CTL responses.
为了发展细胞毒性效应功能，CD8(+) T 淋巴细胞需要在抗原呈递树突状细胞（DC）的共刺激条件下识别特定的 Ag/MHC Ⅰ类复合物。此后，它们分化为效应和记忆 CTL，能够提供针对病原体感染的保护。使用具有 DC 选择性 MHC Ⅰ类表达和 DC 特异性与普遍接种方案的转基因小鼠，我们发现 DC 足以启动 CTL 反应。然而，在实质非专业 APC 上的 Ag 识别通过诱导 CTL 中凋亡蛋白 bcl2 家族成员 bim 的表达，对 CD8(+) T 细胞反应产生负面影响。这种在效应 CTL 积累的早期阶段意外诱导的细胞凋亡导致克隆爆发规模不足和长期记忆减少。因此，我们的数据表明，效应 CTL 分化和凋亡是独立调控的。此外，细胞上除 DC 以外的 Ag 分布会严重降低 CTL 反应。
