Alter, G., Kavanagh, D., Rihn, S. , Luteijn, R., Brooks, D., Oldstone, M., van Lunzen, J. and Altfeld, M. (2010) IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection. Journal of Clinical Investigation, 120(6), pp. 1905-1913. (doi: 10.1172/JCI40913) (PMID:20440075) (PMCID:PMC2877944)
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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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Rihn, Dr Suzannah |
Authors: | Alter, G., Kavanagh, D., Rihn, S., Luteijn, R., Brooks, D., Oldstone, M., van Lunzen, J., and Altfeld, M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | Journal of Clinical Investigation |
Publisher: | American Society for Clinical Investigation |
ISSN: | 0021-9738 |
ISSN (Online): | 1558-8238 |
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