2014
DOI: 10.4049/jimmunol.1302053
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Human Cytomegalovirus Infection Promotes Rapid Maturation of NK Cells Expressing Activating Killer Ig–like Receptor in Patients Transplanted with NKG2C−/− Umbilical Cord Blood

Abstract: NK cells are the first lymphoid population recovering after allogeneic hematopoietic stem cell transplantation and play a crucial role in early immunity after the graft. Recently, it has been shown that human CMV (HCMV) infection/reactivation can deeply influence NK cell reconstitution after umbilical cord blood transplantation by accelerating the differentiation of mature NKG2A−killer Ig-like receptor (KIR)+ NK cells characterized by the expression of the NKG2C-activating receptor. In view of the hypothesis t… Show more

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Cited by 147 publications
(120 citation statements)
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References 45 publications
(66 reference statements)
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“…NKG2C bright NK cells display low levels of NKp30 and NKp46, and preferentially express inhibitory KIR specific for self-HLA-C (15)(16)(17). Recently, HCMV infection has been associated with the expansion of FcεRg-chain-defective NK cells and also with the appearance of NKG2C 2 oligoclonal NK cell subpopulations expressing activating KIR, which further illustrate the pressure exerted by this b-herpesvirus on the host NK cell compartment (16,18,19). The molecular mechanisms driving the HCMV-dependent NK cell differentiation remain unknown.…”
Section: H Uman CMV (Hcmv) Is a B-herpesvirus That Infects 40-mentioning
confidence: 97%
“…NKG2C bright NK cells display low levels of NKp30 and NKp46, and preferentially express inhibitory KIR specific for self-HLA-C (15)(16)(17). Recently, HCMV infection has been associated with the expansion of FcεRg-chain-defective NK cells and also with the appearance of NKG2C 2 oligoclonal NK cell subpopulations expressing activating KIR, which further illustrate the pressure exerted by this b-herpesvirus on the host NK cell compartment (16,18,19). The molecular mechanisms driving the HCMV-dependent NK cell differentiation remain unknown.…”
Section: H Uman CMV (Hcmv) Is a B-herpesvirus That Infects 40-mentioning
confidence: 97%
“…In the absence of NKG2C, activating KIR have been proposed as alternative drivers for HCMV-adaptive NK cell expansions (5,26). Yet, we did not observe a preferential expression of activating KIRs in NKG2C 2 FcRg 2 cells despite the fact that KIR2DS1 and KIR2DS4 were detected among both NKG2C bright FcRg 2 and NKG2C 2 FcRg 2 NK cell subsets.…”
Section: Discussionmentioning
confidence: 99%
“…As mentioned in the initial section, FcRg downregulation was detected in one out of three NKG2C del/del HCMV + individuals (D.#149). Activating KIR were suggested to drive NKG2C-independent adaptive NK cell expansions in patients transplanted with NKG2C del/del hematopoietic grafts undergoing HCMV infection (26). D.#149 was homozygous for KIR-A haplotypes with nonfunctional KIR2DS4 alleles, thus lacking activating KIR besides NKG2C (Fig.…”
Section: Nkg2c Copy Number Is Related To the Redistribution Pattern Omentioning
confidence: 99%
See 1 more Smart Citation
“…It was later demonstrated that these HCMV‐associated NKG2C + NK cells express self‐specific KIRs and account for the vast majority of adult KIR repertoire deviation toward self HLA class I 160. HCMV‐adapted NK cells lacking NKG2C expression were also reported, most of them expressing activating KIRs 160, 161. Using a large NKG2C‐deficient cohort, it was recently demonstrated that adaptive NK cell responses could occur in the absence of both activating KIRs and NKG2C; however, these adaptive NK cells also largely display repertoire deviation toward self‐specific inhibitory KIR expression 162, 163.…”
Section: Kir Gene Expressionmentioning
confidence: 99%