Dataset Information

Loss of CCR7 expression on CD56(bright) NK cells is associated with a CD56(dim)CD16? NK cell-like phenotype and correlates with HIV viral load.

ABSTRACT: NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on CD56(dim)CD16? and CD56?CD16? NK cells. However, the impact of HIV-infection on CD56(bright) NK cells is less well understood. Here we report a rise of CD56(bright) NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. CCR7?CD56(bright) NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of CD56(dim)CD16? NK cells. Furthermore, CD56(bright) NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of CD56(bright) NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment.

SUBMITTER: Hong HS

PROVIDER: S-EPMC3447005 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Loss of CCR7 expression on CD56(bright) NK cells is associated with a CD56(dim)CD16⁺ NK cell-like phenotype and correlates with HIV viral load.

Hong Henoch S HS Ahmad Fareed F Eberhard Johanna M JM Bhatnagar Nupur N Bollmann Benjamin A BA Keudel Phillip P Ballmaier Matthias M Zielinska-Skowronek Margot M Schmidt Reinhold E RE Meyer-Olson Dirk D

PloS one 20120919 9

NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on CD56(dim)CD16⁺ and CD56⁻CD16⁺ NK cells. However, the impact of HIV-infection on CD56(bright) NK cells is less well understood. Here we report a rise of CD56(bright) NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HI ...[more]

PMID: 23028633

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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

Loss of CCR7 expression on CD56(bright) NK cells is associated with a CD56(dim)CD16? NK cell-like phenotype and correlates with HIV viral load.

Publications

Loss of CCR7 expression on CD56(bright) NK cells is associated with a CD56(dim)CD16⁺ NK cell-like phenotype and correlates with HIV viral load.

Similar Datasets

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