Natural killer (NK) cells, influencing dendritic cell (DC)-mediated CD4+ lymphocyte priming in draining lymph nodes (dLNs) and controlling spinal cord (SC) infiltration with encephalitogenic CD4+T lymphocytes, modulate EAE (multiple sclerosis model). This study examined their putative contribution to age-related differences in EAE development in Dark Agouti (DA) (exhibiting age-related decrease in EAE susceptibility) and Albino Oxford (AO) (becoming susceptible to EAE with aging) rats. Aging increased NK cell number in dLNs from rats of both strains. In AO rats, but not in DA ones, it also increased the numbers of IFN-γ-producing NK cells (important for DC activation) and activated/matured DCs, thereby increasing activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated CD25+Foxp3-CD4+ cell number. Aging in DA rats diminished activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated Foxp3-CD4+ cell number. However, MBP-stimulated CD4+ cell proliferation did not differ in dLN cell cultures from young and aged AO rats (as more favorable activated/matured DC/Foxp3-CD4+ cell ratio was abrogated by lower intrinsic CD4+ cell proliferative capacity and a greater regulatory CD25+Foxp3+CD4+ lymphocyte frequency), but was lower in those from aged compared with young DA rats. At SC level, aging shifted Foxp3-CD4+/cytotoxic CX3CR1+ NK cell ratio towards the former in AO rats, so it was less favorable in aged AO rats exhibiting prolonged neurological deficit compared with their DA counterparts. The study showed strain and age differences in number of IFN-γ-producing NK cells in EAE rat dLNs, and suggested that their pathogenetic relevance depends on frequency and/or activity of other cells involved in CD4+ T cell (auto)immune response.

中文翻译：

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天然杀伤细胞参与大鼠实验性自身免疫性脑脊髓炎（EAE）的发病机理：来自不同年龄和品系的大鼠研究的经验教训。

天然杀伤（NK）细胞影响树突状细胞（DC）介导的CD4 +淋巴细胞在引流淋巴结（dLNs）中的启动，并控制具有脑源性CD4 + T淋巴细胞的脊髓（SC）浸润，从而调节EAE（多发性硬化模型）。这项研究检查了他们对黑暗Agouti（DA）（表现出与年龄相关的EAE敏感性降低）和Albino Oxford（AO）（随着年龄增长易受EAE感染）大鼠的EAE发展中与年龄相关的差异的推定贡献。衰老增加了来自两种菌株的大鼠的dLN中的NK细胞数目。在AO大鼠中，但在DA大鼠中却没有，它还增加了产生IFN-γ的NK细胞（对于DC激活很重要）和激活/成熟的DC的数量，从而增加了激活/成熟的DC /常规Foxp3-CD4 +细胞的比例并激活了CD25 + Foxp3-CD4 +细胞号。DA大鼠的衰老减少了活化/成熟的DC /常规Foxp3-CD4 +细胞比例和活化的Foxp3-CD4 +细胞数量。但是，MBP刺激的CD4 +细胞增殖在年轻和老年AO大鼠的dLN细胞培养物中没有区别（因为更有利的活化/成熟DC / Foxp3-CD4 +细胞比率由于较低的固有CD4 +细胞增殖能力和较高的调节性CD25 +而被废除Foxp3 + CD4 +淋巴细胞的频率），但与年轻的DA大鼠相比，在老年患者中较低。在SC水平，衰老使AO大鼠中Foxp3-CD4 + /细胞毒性CX3CR1 + NK细胞的比例朝前者方向移动，因此，与DA相对应的衰老相比，衰老的AO大鼠表现出较长的神经功能缺损。研究显示，EAE大鼠dLNs中产生IFN-γ的NK细胞数量上的株和年龄差异，