Qa-1b-Dependent Modulation of Dendritic Cell and NK Cell Cross-Talk In Vivo

• Published in: The Journal of immunology (1950) Vol. 179; no. 7; pp. 4608 - 4615
• Main Authors: Colmenero, Paula, Zhang, Angela L, Qian, Ting, Lu, Linrong, Cantor, Harvey, Soderstrom, Kalle, Engleman, Edgar G
• Format: Journal Article
• Language: English
• Published: Am Assoc Immnol 01.10.2007
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.179.7.4608

Abstract Dendritic cells (DC) trigger activation and IFN-γ 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-γ synthesis. In this study, we analyzed whether the interaction between Qa-1b expressed on DC and its CD94/NKG2A receptor on NK cells affects this process. Activation of DC using CpG-oligodeoxynucleotides in Qa-1b-deficient mice, or transfer of CpG-oligodeoxynucleotide-activated Qa-1b-deficient DC into wild-type mice, resulted in dramatically increased IFN-γ production by NK cells, as compared with that induced by Qa-1b-expressing DC. Masking the CD94/NKG2A inhibitory receptor on NK cells in wild-type mice similarly enhanced the IFN-γ response of these cells to Qa-1b-expressing DC. Furthermore, NK cells from CD94/NKG2A-deficient mice displayed higher IFN-γ production upon DC stimulation. These results demonstrate that Qa-1b is critically involved in regulating IFN-γ 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.