TY - JOUR
T1 - Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function
AU - Foley, Bree
AU - Cooley, Sarah
AU - Verneris, Michael R.
AU - Pitt, Michelle
AU - Curtsinger, Julie
AU - Luo, Xianghua
AU - Lopez-Vergès, Sandra
AU - Lanier, Lewis L.
AU - Weisdorf, Daniel
AU - Miller, Jeffrey S.
PY - 2012/3/15
Y1 - 2012/3/15
N2 - 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,andself-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-15RαmRNA 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.
AB - 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,andself-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-15RαmRNA 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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U2 - 10.1182/blood-2011-10-386995
DO - 10.1182/blood-2011-10-386995
M3 - Article
C2 - 22180440
AN - SCOPUS:84863338121
SN - 0006-4971
VL - 119
SP - 2665
EP - 2674
JO - Blood
JF - Blood
IS - 11
ER -