Year: 2019
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Human cytomegalovirus (CMV) reactivation is a common occurrence early after transplant and is associated with heterogeneous NK cell subset expansion. These adaptive NK cell expansions are highly variable between recipients, with respect to magnitude and relative frequencies of adaptive NK cell subsets. METHODS: To gain insight into the factors that influence adaptive NK cell expansion from a CMV naive graft source, we performed a high-resolution NK cell and CD8+ T cell phenotypic analysis of 215 patients with hematological malignancies that were transplanted with 2 partially HLA matched CMV negative umbilical cord blood units. RESULTS: We found that adaptive NK cells were significantly higher in recipients who received nonmyeloablative conditioning (NMAC) relative to myeloablative conditioning (MAC), and high CMV neutralizing antibody titers correlated with the degree of adaptive NK cell expansion. The frequencies of adaptive NK cell subsets (defined by NKG2C, FcεRγ, EAT-2, and SYK expression) that reconstitute from donor hematopoietic progenitor cells largely matched the frequencies observed in the NK cell compartment of the recipient prior to conditioning, suggesting that host - as well as viral reactivation factors - may determine the phenotypic diversification after transplant. Additionally, multivariable analyses show that higher adaptive NK cell expansion associated with better disease-free survival. CONCLUSIONS: Our findings provide important insights into adaptive NK cell reconstitution after transplant and support a role for adaptive NK cells in promoting better clinical outcomes. FUNDING: The NIH and the National Marrow Donor Program.
Source: JCI Insight
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: G1345980661, G1515985705, G1905428511, G203915563, Control of CMV infection post-HCT using attenuated MVA-based CMV subunit vaccine, G2528628858, G2882239208, G2935575925, G345720138, Molecular Programming of Immunological Memory in Human Natural Killer Cells, G3845059438, G429813519, G4906268028, HCMV Vaccine produced from BAC-MVA that Blocks Epithelial and Fibroblast Entry, G5334883042, G5700729068, G609966341, G6830333960, G6937668297, G7617913960, G772794905, G7818486124, G795823422, G9000020151, G9000051389, G9000062357, G9000062628, G9000092632, G9000102014, G9000102636, G9000165233, G9000165770, G9000263201, G9000323903, G9000325690, G9000327612, Cancer Center Support Grant
OpenAlex ID: W2914128979