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IL-12-producing monocytes and HLA-E control HCMV-driven NKC2C+ NK cell expansion.
- Source :
-
Journal of Clinical Investigation . Dec2014, Vol. 124 Issue 12, p5305-5316. 12p. 3 Charts, 6 Graphs. - Publication Year :
- 2014
-
Abstract
- Human cytomegalovirus (HCMV) infection is the most common cause of congenital viral infections and a major source of morbidity and mortality after organ transplantation. NK cells are pivotal effector cells in the innate defense against CMV. Recently, hallmarks of adaptive responses, such as memory-like features, have been recognized in NK cells. HCMV infection elicits the expansion of an NK cell subset carrying an activating receptor heterodimer, comprising CD94 and NKG2C (CD94/ NKG2C), a response that resembles the clonal expansion of adaptive immune cells. Here, we determined that expansion of this NKG2C+ subset and general NK cell recovery rely on signals derived from CD14+ monocytes. In a coculture system, a subset of CD14+ cells with inflammatory monocyte features produced IL-12 in response to HCMV-infected fibroblasts, and neutralization of IL-12 in this model substantially reduced CD25 upregulation and NKG2C+ subset expansion. Finally, blockade of CD94/NKG2C on NK cells or silencing of the cognate ligand HLA-E in infected fibroblasts greatly impaired expansion of NKG2C+ NK cells. Together, our results reveal that IL-12, CD14+ cells, and the CD94/NKG2C/HLA-E axis are critical for the expansion of NKG2C+ NK cells in response to HCMV infection. Moreover, strategies targeting the NKG2C+ NK cell subset have the potential to be exploited in NK cell-based intervention strategies against viral infections and cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 124
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 99847583
- Full Text :
- https://doi.org/10.1172/JCI77440