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Amplified NKG2C+NK Cells in Cytomegalovirus (CMV) Infection Preferentially Express Killer Cell Ig-like Receptor 2DL: Functional Impact in Controlling CMV-Infected Dendritic Cells

Abstract : 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.
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https://www.hal.inserm.fr/inserm-03291384
Contributor : Christelle Retiere Connect in order to contact the contributor
Submitted on : Monday, July 19, 2021 - 5:14:05 PM
Last modification on : Friday, September 17, 2021 - 10:28:02 AM
Long-term archiving on: : Wednesday, October 20, 2021 - 7:22:30 PM

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Zakia Djaoud, Gaëlle David, Céline Bressollette, Catherine Willem, Pauline Rettman, et al.. Amplified NKG2C+NK Cells in Cytomegalovirus (CMV) Infection Preferentially Express Killer Cell Ig-like Receptor 2DL: Functional Impact in Controlling CMV-Infected Dendritic Cells. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2013, 191 (5), pp.2708 - 2716. ⟨10.4049/jimmunol.1301138⟩. ⟨inserm-03291384⟩

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