Dataset Information

Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation.

ABSTRACT: The two major functions of human natural killer (NK) cells are conventionally associated with distinct cell subsets. Thus, cytolytic activity is mostly confined to the CD56(dim)CD16(+) subset, whereas cytokine production is generally assigned to CD56(bright)CD16(+/-) cells. In this study, we reevaluated the functional capabilities of these NK subsets with regard to the production of IFN-? at different time points after cell triggering via NKp46 and NKp30 activating receptors. Different from previous studies, cytokine production was also assessed at early intervals. We show that CD56(dim) NK cells produce IFN-? already at 2 to 4 h, whereas no cytokine production is detected beyond 16 h. In contrast, CD56(bright) cells release IFN-? only at late time intervals (>16 h after stimulation). The rapid IFN-? production by CD56(dim) NK cells is in line with the presence of IFN-? mRNA in freshly isolated cells. Rapid IFN-? production was also induced by combinations of IL-2, IL-12, and IL-15. Our data indicate that not only cytolytic activity but also early IFN-? production is a functional property of CD56(dim) NK cells. Thus, this subset can assure a rapid and comprehensive NK cell intervention during the early phases of innate responses.

SUBMITTER: De Maria A

PROVIDER: S-EPMC3021076 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation.

De Maria Andrea A Bozzano Federica F Cantoni Claudia C Moretta Lorenzo L

Proceedings of the National Academy of Sciences of the United States of America 20101227 2

The two major functions of human natural killer (NK) cells are conventionally associated with distinct cell subsets. Thus, cytolytic activity is mostly confined to the CD56(dim)CD16(+) subset, whereas cytokine production is generally assigned to CD56(bright)CD16(+/-) cells. In this study, we reevaluated the functional capabilities of these NK subsets with regard to the production of IFN-γ at different time points after cell triggering via NKp46 and NKp30 activating receptors. Different from prev ...[more]

PMID: 21187373

Similar Datasets

Project description:Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-α2b (HDI) on the circulatory NK cell profile in melanoma patients. At baseline, patient NK cells, particularly those isolated from high-risk patients with no measurable disease, showed altered distribution of CD56dim CD16+ and CD56dim CD16- NK cell subsets, as well as elevated serum levels of immune suppressive MICA, TN5E/CD73 and tactile/CD96, and perforin. Surprisingly, patient NK cells displayed a higher level of activation than those from healthy donors as measured by elevated CD69, NKp44 and CCR7 levels, and enhanced K562 killing. Elevated cytolytic ability strongly correlated with increased representation of CD56dim CD16+ NK cells and amplified CD69 expression on CD56dim CD16+ NK cells. While intradermal DC immunizations did not significantly impact circulatory NK cell activation and distribution profiles, subsequent HDI injections enhanced CD56bright CD16- NK cell numbers when compared to patients that did not receive HDI. Phenotypic analysis of tumor-infiltrating NK cells showed that CD56dim CD16- NK cells are the dominant subset in melanoma tumors. NanoString transcriptomic analysis of melanomas resected at baseline indicated that there was a trend of increased CD56dim NK cell gene signature expression in patients with better clinical response. These data indicate that melanoma patient blood NK cells display elevated activation levels, that intra-dermal DC immunizations did not effectively promote systemic NK cell responses, that systemic HDI administration can modulate NK cell subset distributions and suggest that CD56dim CD16- NK cells are a unique non-cytolytic subset in melanoma patients that may associate with better patient outcome.

Dataset Information

Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation.

Publications

Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets