| First Author | Ortaldo JR | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 4 | Pages | 1468-75 |
| PubMed ID | 16249390 | Mgi Jnum | J:129310 |
| Mgi Id | MGI:3769057 | Doi | 10.1182/blood-2005-04-1579 |
| Citation | Ortaldo JR, et al. (2006) Regulation of ITAM-positive receptors: role of IL-12 and IL-18. Blood 107(4):1468-75 |
| abstractText | Our previous studies have identified mechanisms by which cytokine production, blocked by Ly49G2 receptor cross-linking, can be overridden. In this study we analyzed the regulation of other ITAM-positive receptor signaling on NK, NKT, and T cells and characterized the biochemical pathways involved in this signaling. Our studies demonstrate that cross-linking of NKG2D and NK1.1 results in a synergistic NK IFN-gamma response when combined with IL-12 or IL-18. Examination of NKT- and T-cell responses demonstrated that cross-linking of NKG2D and CD3 resulted in potent synergy when combined with IL-12 and, to a lesser degree, with IL-18. We have now found that both the p38 MAP kinase and the ERK-dependent signal transduction pathways are required for the synergistic response. Further mechanistic examination of the synergy indicated a potent up-regulation of total IFN-gamma mRNA in the nuclear and the cytoplasmic compartment, but mRNA half-life was not affected. Fifteen minutes of IL-12 pretreatment was sufficient to result in maximal synergistic activation, indicating that the response of the cells to the IL-12 signal was rapid and immediate. Thus, our data demonstrate that multiple convergent signals maximize the innate immune response by triggering complementary biochemical signaling pathways. |
