Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 07239.
J Immunol. 2013 Oct 1;191(7):3663-72. doi: 10.4049/jimmunol.1301328. Epub 2013 Sep 4.
NF-κB-inducing kinase [(NIK), MAP3K14] is an essential kinase linking a subset of TNFR family members to the noncanonical NF-κB pathway. To assess the cell-intrinsic role of NIK in murine T cell function, we generated mixed bone marrow chimeras using bone marrow from NIK knockout (KO) and wild-type (WT) donor mice and infected the chimeras with lymphocytic choriomeningitis virus (LCMV). The chimeras possess an apparently normal immune system, including a mixture of NIK KO and WT T cells, and the virus was cleared normally. Comparison of the NIK KO and WT CD4 and CD8 T cell responses at 8 d post infection revealed modest but significant differences in the acute response. In both CD4 and CD8 compartments, relatively fewer activated (CD44(hi)) NIK KO T cells were present, but within the CD44(hi) population, a comparable percentage of the activated cells produced IFN-γ in response to ex vivo stimulation with antigenic LCMV peptides, although IL-7R expression was reduced in the NIK KO CD8 T cells. Assessment of the LCMV-specific memory at 65 d post infection revealed many more LCMV-specific WT memory T cells than NIK KO memory T cells in both the CD4 and the CD8 compartments, although the small number of surviving NIK KO memory T cells responded to secondary challenge with virus. These results demonstrate a cell-intrinsic requirement for NIK in the generation and/or maintenance of memory T cells in response to acute viral infection.
NF-κB 诱导激酶 [(NIK)，MAP3K14] 是一种将 TNFR 家族成员的一部分与非经典 NF-κB 途径连接起来的必需激酶。为了评估 NIK 在小鼠 T 细胞功能中的细胞内在作用，我们使用 NIK 敲除 (KO) 和野生型 (WT) 供体骨髓生成混合骨髓嵌合体，并将嵌合体感染淋巴细胞性脉络丛脑膜炎病毒 (LCMV)。嵌合体具有明显正常的免疫系统，包括 NIK KO 和 WT T 细胞的混合物，并且病毒正常清除。感染后 8 天比较 NIK KO 和 WT CD4 和 CD8 T 细胞反应，发现急性反应中存在适度但显著的差异。在 CD4 和 CD8 两个区室中，存在的激活（CD44(hi)）NIK KO T 细胞相对较少，但在 CD44(hi)群体中，相同比例的激活细胞在体外用抗原性 LCMV 肽刺激时产生 IFN-γ，尽管 NIK KO CD8 T 细胞中的 IL-7R 表达减少。在感染后 65 天评估 LCMV 特异性记忆时，发现在 CD4 和 CD8 两个区室中，与 NIK KO 记忆 T 细胞相比，存在更多的 LCMV 特异性 WT 记忆 T 细胞，尽管存活的 NIK KO 记忆 T 细胞数量较少，但对病毒的二次挑战有反应。这些结果表明，在急性病毒感染中，NIK 在记忆 T 细胞的产生和/或维持中具有细胞内在的要求。
