Colmenero Paula, Zhang Angela L, Qian Ting, Lu Linrong, Cantor Harvey, Söderström Kalle, Engleman Edgar G
Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
J Immunol. 2007 Oct 1;179(7):4608-15. doi: 10.4049/jimmunol.179.7.4608.
Dendritic cells (DC) trigger activation and IFN-gamma release by NK cells in lymphoid tissues, a process important for the polarization of Th1 responses. Little is known about the molecular signals that regulate DC-induced NK cell IFN-gamma synthesis. In this study, we analyzed whether the interaction between Qa-1(b) expressed on DC and its CD94/NKG2A receptor on NK cells affects this process. Activation of DC using CpG-oligodeoxynucleotides in Qa-1(b)-deficient mice, or transfer of CpG-oligodeoxynucleotide-activated Qa-1(b)-deficient DC into wild-type mice, resulted in dramatically increased IFN-gamma production by NK cells, as compared with that induced by Qa-1(b)-expressing DC. Masking the CD94/NKG2A inhibitory receptor on NK cells in wild-type mice similarly enhanced the IFN-gamma response of these cells to Qa-1(b)-expressing DC. Furthermore, NK cells from CD94/NKG2A-deficient mice displayed higher IFN-gamma production upon DC stimulation. These results demonstrate that Qa-1(b) is critically involved in regulating IFN-gamma synthesis by NK cells in vivo through its interaction with CD94/NKG2A inhibitory receptors. This receptor-ligand interaction may be essential to prevent unabated cytokine production by NK cells during an inflammatory response.
树突状细胞（DC）在淋巴组织中触发自然杀伤细胞（NK细胞）的激活及γ干扰素释放，这一过程对Th1反应的极化至关重要。关于调节DC诱导的NK细胞γ干扰素合成的分子信号，人们了解甚少。在本研究中，我们分析了DC上表达的Qa-1(b)与其NK细胞上的CD94/NKG2A受体之间的相互作用是否会影响这一过程。在Qa-1(b)缺陷小鼠中使用CpG-寡脱氧核苷酸激活DC，或将CpG-寡脱氧核苷酸激活的Qa-1(b)缺陷DC转移到野生型小鼠中，与表达Qa-1(b)的DC诱导的情况相比，会导致NK细胞产生的γ干扰素显著增加。在野生型小鼠中阻断NK细胞上的CD94/NKG2A抑制性受体同样增强了这些细胞对表达Qa-1(b)的DC的γ干扰素反应。此外，来自CD94/NKG2A缺陷小鼠的NK细胞在DC刺激下表现出更高的γ干扰素产生。这些结果表明，Qa-1(b)通过与CD94/NKG2A抑制性受体相互作用，在体内对调节NK细胞的γ干扰素合成起关键作用。这种受体-配体相互作用对于在炎症反应期间防止NK细胞不受控制地产生细胞因子可能至关重要。
