Earle A. Chiles Research Institute, Robert W Franz Cancer Research Center, Providence Cancer Center, Portland, Oregon, United States of America.
PLoS One. 2013 May 23;8(5):e64878. doi: 10.1371/journal.pone.0064878. Print 2013.
The ability of memory CD8+ T cells to rapidly proliferate and acquire cytolytic activity is critical for protective immunity against intracellular pathogens. The signals that control this recall response remain unclear. We show that CD40L production by memory CD8+ T cells themselves is an essential catalyst for secondary expansion when systemic inflammation is limited. Secondary immunization accompanied by high levels of systemic inflammation results in CD8+ T cell secondary expansion independent of CD4+ T cells and CD40-CD40L signaling. Conversely, when the inflammatory response is limited, memory CD8+ T cell secondary expansion requires CD40L-producing cells, and memory CD8+ T cells can provide this signal. These results demonstrate that vaccination regimens differ in their dependence on CD40L-expressing CD8+ T cells for secondary expansion, and propose that CD40L-expression by CD8+ T cells is a fail-safe mechanism that can promote memory CD8+ T cell secondary expansion when inflammation is limited.
记忆性 CD8+T 细胞迅速增殖并获得细胞毒活性的能力对于针对细胞内病原体的保护性免疫至关重要。控制这种回忆反应的信号仍不清楚。我们表明，当全身炎症受到限制时，记忆性 CD8+T 细胞自身产生 CD40L 是二次扩增的关键催化剂。伴随着高水平全身炎症的二次免疫导致 CD8+T 细胞的二次扩增不依赖于 CD4+T 细胞和 CD40-CD40L 信号传导。相反，当炎症反应受到限制时，记忆性 CD8+T 细胞的二次扩增需要产生 CD40L 的细胞，并且记忆性 CD8+T 细胞可以提供这种信号。这些结果表明，疫苗接种方案在其对 CD40L 表达的 CD8+T 细胞进行二次扩增的依赖性上存在差异，并提出 CD8+T 细胞表达 CD40L 是一种故障安全机制，当炎症受到限制时，它可以促进记忆性 CD8+T 细胞的二次扩增。
