Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function

B Foley, S Cooley, MR Verneris, M Pitt… - Blood, The Journal …, 2012 - ashpublications.org
B Foley, S Cooley, MR Verneris, M Pitt, J Curtsinger, X Luo, S Lopez-Vergès, LL Lanier
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
During mouse cytomegalovirus (CMV) infection, a population of Ly49H+ natural killer (NK)
cells expands and is responsible for disease clearance through the induction of a “memory
NK-cell response.” Whether similar events occur in human CMV infection is unknown. In the
present study, we characterized the kinetics of the NK-cell response to CMV reactivation in
human recipients after hematopoietic cell transplantation. During acute infection, NKG2C+
NK cells expanded and were potent producers of IFNγ. NKG2C+ NK cells predominately …
Abstract
During mouse cytomegalovirus (CMV) infection, a population of Ly49H+ natural killer (NK) cells expands and is responsible for disease clearance through the induction of a “memory NK-cell response.” Whether similar events occur in human CMV infection is unknown. In the present study, we characterized the kinetics of the NK-cell response to CMV reactivation in human recipients after hematopoietic cell transplantation. During acute infection, NKG2C+ NK cells expanded and were potent producers of IFNγ. NKG2C+ NK cells predominately expressed killer cell immunoglobulin–like receptor, and self-killer cell immunoglobulin–like receptors were required for robust IFNγ production. During the first year after transplantation, CMV reactivation induced a more mature phenotype characterized by an increase in CD56dim NK cells. Strikingly, increased frequencies of NKG2C+ NK cells persisted and continued to increase in recipients who reactivated CMV, whereas these cells remained at low frequency in recipients without CMV reactivation. Persisting NKG2C+ NK cells lacked NKG2A, expressed CD158b, preferentially acquired CD57, and were potent producers of IFNγ during the first year after transplantation. Recipients who reactivated CMV also expressed higher amounts of IFNγ, T-bet, and IL-15Rα mRNA transcripts. Our findings support the emerging concept that CMV-induced innate memory-cell populations may contribute to malignant disease relapse protection and infectious disease control long after transplantation.
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