| First Author | Sepulveda FE | Year | 2015 |
| Journal | Blood | Volume | 125 |
| Issue | 9 | Pages | 1427-34 |
| PubMed ID | 25525117 | Mgi Jnum | J:221376 |
| Mgi Id | MGI:5638987 | Doi | 10.1182/blood-2014-09-602946 |
| Citation | Sepulveda FE, et al. (2015) A novel immunoregulatory role for NK-cell cytotoxicity in protection from HLH-like immunopathology in mice. Blood 125(9):1427-34 |
| abstractText | The impairment of cytotoxic activity of lymphocytes disturbs immune surveillance and leads to the development of hemophagocytic lymphohistiocytic syndrome (HLH). Although cytotoxic T lymphocyte (CTL) control of HLH development is well documented, the role for natural killer (NK)-cell effector functions in the pathogenesis of this immune disorder remains unclear. In this study, we specifically targeted a defect in cytotoxicity to either CTL or NK cells in mice so as to dissect the contribution of these lymphocyte subsets to HLH-like disease severity after lymphocytic choriomeningitis virus (LCMV) infection. We found that NK-cell cytotoxicity was sufficient to protect mice from the fatal outcome that characterizes HLH-like disease and was also sufficient to reduce HLH-like manifestations. Mechanistically, NK-cell cytotoxicity reduced tissue infiltration by inflammatory macrophages and downmodulated LCMV-specific T-cell responses by limiting hyperactivation of CTL. Interestingly, the critical protective effect of NK cells on HLH was independent of interferon-gamma secretion and changes in viral load. Therefore our findings identify a crucial role of NK-cell cytotoxicity in limiting HLH-like immunopathology, highlighting the important role of NK cytotoxic activity in immune homeostasis. |
