Division of Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 2013 May 1;190(9):4754-62. doi: 10.4049/jimmunol.1201742. Epub 2013 Mar 25.
Several recent studies have demonstrated that innate immune NK cells exhibit memory-like properties with enhanced nonspecific and specific recall responses. Cytokine activation alone of murine NK cells induces the differentiation of memory-like cells that are more likely to produce IFN-γ, a key NK cell cytokine important for activation of the immune response. Using an adoptive cotransfer system, we first show that cytokine-induced memory-like responses are NK intrinsic. However, engraftment of donor NK cells in NK-competent hosts is poor because of homeostatic control mechanisms. Therefore, we used alymphoid Rag- and common γ-chain-deficient mice as recipients and observed homeostatic expansion of cotransferred cytokine-activated and control donor NK cells. Despite proliferation of all cells, NK cells derived from those cells originally activated by cytokines retained an intrinsic enhanced capacity to produce IFN-γ when restimulated in vitro with cytokines or target cells. These NK cell memory-like responses persisted for at least 4 wk in alymphoid hosts and 12 wk in NK-competent hosts. These findings indicate that memory-like NK cells can readily self-renew and maintain enhanced function in a lymphopenic host for at least a month.
几项最近的研究表明，天然免疫 NK 细胞表现出记忆样特性，具有增强的非特异性和特异性回忆反应。单独的细胞因子激活可诱导产生记忆样细胞，这些细胞更可能产生 IFN-γ，IFN-γ 是一种关键的 NK 细胞细胞因子，对免疫反应的激活很重要。我们首先使用过继共转移系统，表明细胞因子诱导的记忆样反应是 NK 细胞内在的。然而，由于体内平衡控制机制，供体 NK 细胞在 NK 细胞功能正常的宿主中的植入效果较差。因此，我们使用无淋巴细胞 Rag 和常见 γ 链缺陷小鼠作为受体，并观察到共转移的细胞因子激活和对照供体 NK 细胞的体内平衡扩增。尽管所有细胞都增殖，但当用细胞因子或靶细胞再次刺激时，源自最初被细胞因子激活的细胞的 NK 细胞仍然具有内在的增强产生 IFN-γ 的能力。在无淋巴细胞宿主中，这种 NK 细胞记忆样反应至少持续 4 周，在 NK 细胞功能正常的宿主中持续 12 周。这些发现表明，记忆样 NK 细胞可以在至少一个月的淋巴减少宿主中容易地自我更新并保持增强的功能。
