Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia.
J Immunol. 2011 Aug 1;187(3):1385-92. doi: 10.4049/jimmunol.1100416. Epub 2011 Jun 22.
NK cells recognize virus-infected cells with germline-encoded activating and inhibitory receptors that do not undergo genetic recombination or mutation. Accordingly, NK cells are often considered part of the innate immune response. The innate response comprises rapid early defenders that do not form immune memory. However, there is increasing evidence that experienced NK cells provide increased protection to secondary infection, a hallmark of the adaptive response. In this study, we compare the dynamics of the innate and adaptive immune responses by examining the kinetic profiles of the NK and T cell response to murine CMV infection. We find that, unexpectedly, the kinetics of NK cell proliferation is neither earlier nor faster than the CD4 or CD8 T cell response. Furthermore, early NK cell contraction after the peak of the response is slower than that of T cells. Finally, unlike T cells, experienced NK cells do not experience biphasic decay after the response peak, a trait associated with memory formation. Rather, NK cell contraction is continuous, constant, and returns to below endogenous preinfection levels. This indicates that the reason why Ag-experienced NK cells remain detectable for a prolonged period after adoptive transfer and infection is in part due to the high precursor frequency, slow decay rate, and low background levels of Ly49H(+) NK cells in recipient DAP12-deficient mice. Thus, the quantitative contribution of Ag-experienced NK cells in an endogenous secondary response, with higher background levels of Ly49H(+) NK cells, may be not be as robust as the secondary response observed in T cells.
NK 细胞通过胚系编码的激活和抑制受体识别病毒感染的细胞，这些受体不经历基因重组或突变。因此，NK 细胞通常被认为是固有免疫反应的一部分。固有反应包括不形成免疫记忆的快速早期防御者。然而，越来越多的证据表明，经验丰富的 NK 细胞为二次感染提供了更大的保护，这是适应性反应的一个标志。在这项研究中，我们通过检查 NK 和 T 细胞对鼠 CMV 感染的反应动力学特征，比较了固有免疫和适应性免疫反应的动力学。我们发现，出乎意料的是，NK 细胞增殖的动力学既不比 CD4 或 CD8 T 细胞反应更早也不快。此外，在反应高峰后，早期 NK 细胞的收缩比 T 细胞慢。最后，与 T 细胞不同，经验丰富的 NK 细胞在反应高峰后不会经历双峰衰减，这是与记忆形成相关的特征。相反，NK 细胞的收缩是连续的、恒定的，并恢复到低于内源性感染前水平。这表明，Ag 经验丰富的 NK 细胞在过继转移和感染后能够长时间被检测到的部分原因是，在缺乏 DAP12 的受体小鼠中，NK 细胞的 Ly49H(+)前体频率高、衰减率慢、背景水平低。因此，在背景水平较高的 Ly49H(+)NK 细胞中，Ag 经验丰富的 NK 细胞在体内二次反应中的定量贡献可能不如 T 细胞中观察到的二次反应那样显著。
