IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection.
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IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection. / Alter, Galit; Kavanagh, Daniel; Rihn, Suzannah; Luteijn, Rutger; Brooks, David; Oldstone, Michael; van Lunzen, Jan; Altfeld, Marcus.
in: J CLIN INVEST, Jahrgang 120, Nr. 6, 6, 2010, S. 1905-1913.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection.
AU - Alter, Galit
AU - Kavanagh, Daniel
AU - Rihn, Suzannah
AU - Luteijn, Rutger
AU - Brooks, David
AU - Oldstone, Michael
AU - van Lunzen, Jan
AU - Altfeld, Marcus
PY - 2010
Y1 - 2010
N2 - Persistent levels of IL-10 play a central role in progressive immune dysfunction associated with chronic viral infections such as HIV, but the underlying mechanisms are poorly understood. Because IL-10 affects the phenotypic and functional properties of DCs, which are responsible for initiating adaptive immune responses, we investigated whether IL-10 induces changes in DC phenotype and function in the context of HIV infection. Here, we show that IL-10 treatment of immature and mature human DCs in culture induced contrasting phenotypic changes in these populations: immature DCs exhibited aberrant resistance to NK cell-mediated elimination, whereas mature DCs exhibited increased susceptibility to NKG2D-dependent NK elimination. Treatment of immature and mature DCs with HIV resulted in potent IL-10 secretion and the same phenotypic and functional changes observed in the IL-10-treated cells. Consistent with these in vitro data, LNs isolated from individuals infected with HIV exhibited aberrant accumulation of a partially "immature" DC population. Together, these data suggest that the progressive immune dysfunction observed in chronic viral infections might be caused in part by IL-10-induced reversal of DC susceptibility to NK cell-mediated elimination, resulting in the accumulation of poorly immunogenic DCs in LNs, the sites of adaptive immune response induction.
AB - Persistent levels of IL-10 play a central role in progressive immune dysfunction associated with chronic viral infections such as HIV, but the underlying mechanisms are poorly understood. Because IL-10 affects the phenotypic and functional properties of DCs, which are responsible for initiating adaptive immune responses, we investigated whether IL-10 induces changes in DC phenotype and function in the context of HIV infection. Here, we show that IL-10 treatment of immature and mature human DCs in culture induced contrasting phenotypic changes in these populations: immature DCs exhibited aberrant resistance to NK cell-mediated elimination, whereas mature DCs exhibited increased susceptibility to NKG2D-dependent NK elimination. Treatment of immature and mature DCs with HIV resulted in potent IL-10 secretion and the same phenotypic and functional changes observed in the IL-10-treated cells. Consistent with these in vitro data, LNs isolated from individuals infected with HIV exhibited aberrant accumulation of a partially "immature" DC population. Together, these data suggest that the progressive immune dysfunction observed in chronic viral infections might be caused in part by IL-10-induced reversal of DC susceptibility to NK cell-mediated elimination, resulting in the accumulation of poorly immunogenic DCs in LNs, the sites of adaptive immune response induction.
KW - Humans
KW - HIV Infections immunology
KW - Cell Differentiation immunology
KW - Dendritic Cells cytology
KW - HIV immunology
KW - Interleukin-10 immunology
KW - Killer Cells, Natural immunology
KW - Humans
KW - HIV Infections immunology
KW - Cell Differentiation immunology
KW - Dendritic Cells cytology
KW - HIV immunology
KW - Interleukin-10 immunology
KW - Killer Cells, Natural immunology
M3 - SCORING: Zeitschriftenaufsatz
VL - 120
SP - 1905
EP - 1913
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 6
M1 - 6
ER -