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IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection
Galit Alter, … , Jan van Lunzen, Marcus Altfeld
Galit Alter, … , Jan van Lunzen, Marcus Altfeld
Published May 3, 2010
Citation Information: J Clin Invest. 2010;120(6):1905-1913. https://doi.org/10.1172/JCI40913.
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Research Article Virology

IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection

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Abstract

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.

Authors

Galit Alter, Daniel Kavanagh, Suzannah Rihn, Rutger Luteijn, David Brooks, Michael Oldstone, Jan van Lunzen, Marcus Altfeld

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Figure 1

Accumulation of aberrant DC populations in the LNs of HIV-infected individuals.

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Accumulation of aberrant DC populations in the LNs of HIV-infected indiv...
Shown are mean ± SEM of (A) HLA-DR and HLA-I (i.e., HLA-A, -B, or -C) and (B) costimulatory molecules CD40, CD83, CD80, and CD86 on the surface of CD3–CD14–CD56–CD11c+ DCs in PBMCs and LNs from HIV-infected and HIV-negative donors. *P < 0.05.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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