Amplified NKG2C+ NK cells in cytomegalovirus (CMV) infection preferentially express killer cell Ig-like receptor 2DL: functional impact in controlling CMV-infected dendritic cells

• Published in: The Journal of immunology (1950) 2013-09, Vol.191 (5), p.2708-2716
• Main Authors: Djaoud, Zakia, David, Gaëlle, Bressollette, Céline, Willem, Catherine, Rettman, Pauline, Gagne, Katia, Legrand, Nolwenn, Mehlal, Souad, Cesbron, Anne, Imbert-Marcille, Berthe-Marie, Retière, Christelle
• Format: Article
• Language: English
• Subjects: Cellular Biology; Cytomegalovirus; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - metabolism; Dendritic Cells - immunology; Dendritic Cells - virology; Flow Cytometry; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Humans; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Life Sciences; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; NK Cell Lectin-Like Receptor Subfamily C - immunology; NK Cell Lectin-Like Receptor Subfamily C - metabolism; Receptors, KIR - biosynthesis; Receptors, KIR - immunology; Receptors, KIR2DL1 - biosynthesis; Receptors, KIR2DL1 - immunology; Receptors, KIR2DL3 - biosynthesis; Receptors, KIR2DL3 - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1301138

CMV infection represents a major complication in hematopoietic stem cell transplantation, which compromises graft outcome. Downregulation of HLA class I expression is one mechanism by which CMV evades T cell-mediated immune detection, rendering infected cells vulnerable to killer cell Ig-like receptor (KIR)(+) NK cells. In this study, we observed that the amplified NKG2C(+) NK cell population observed specifically in CMV seropositive individuals mainly expressed KIR2DL receptors. We have shown that HLA class I expression was downregulated on CMV-infected immature dendritic cells (iDCs), which escape to HLA-A2-pp65-specific T lymphocytes but strongly trigger the degranulation of KIR2D(+) NK cells. CMV infection conferred a vulnerability of C2C2(+) iDCs to educated KIR2DL1(+) and KIR2DL3(+) NK cell subsets. Alloreactivity of KIR2DL1(+) NK cell subsets against C1C1(+) iDCs was maintained independently of CMV infection. Unexpectedly, CMV-infected C1C1(+) iDCs did not activate KIR2DL3(+) NK cell reactivity, suggesting a potential CMV evasion to KIR2DL3 NK cell recognition. Altogether, the coexpression of KIR and NKG2C on expanded NK cell subsets could be related to a functional contribution of KIR in CMV infection and should be investigated in hematopoietic stem cell transplantation, in which the beneficial impact of CMV infection has been reported on the graft-versus-leukemia effect.