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Cutting Edge: Antioxidative Properties of Myeloid Dendritic Cells: Protection of T Cells and NK Cells from Oxygen Radical-Induced Inactivation and Apoptosis¹

Department of Infectious Medicine, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

Dendritic cells (DCs) communicate with nonadaptive and adaptive lymphocytes on multiple levels. Efficient DC-lymphocyte interactions require that lymphocytes remain viable and functional also under conditions of oxidative stress, such as in microbial infection or in the malignant microenvironment. For this study, we exposed human T and NK cells to oxidants delivered either by autologous phagocytes or in the form of exogenous hydrogen peroxide. In accordance with earlier studies, these lymphocytes became dysfunctional and subsequently apoptotic. The presence of myeloid DCs efficiently rescued T cells (CD4⁺ and CD8⁺) and NK cells from oxidant-induced inactivation and apoptosis. The mechanism of the myeloid DC-mediated lymphocyte protection was, at least in part, explained by the capacity of the myeloid DCs to neutralize extracellular oxygen radicals, which, in turn, was reversible upon coincubation with a catalase inhibitor. Our results are suggestive of a novel aspect of DC-lymphocyte interaction that may have implications for lymphocyte function in inflamed tissue.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by the Swedish Cancer Society, the Swedish Research Council, the Inga-Britt and Arne Lundberg Research Foundation, and the Sahlgrenska Academy at Göteborg University.

² Address correspondence and reprint requests to Dr. Kristoffer Hellstrand, Department of Infectious Medicine, Göteborg University, Guldhedsgatan 10b, S-413 46 Göteborg, Sweden. E-mail address: kristoffer.hellstrand{at}microbio.gu.se

³ Abbreviations used in this paper: DC, dendritic cell; adMP, adherent mononuclear phagocyte; ALM-633, Alexa Fluor 633-coupled maleimide; 3-AT, 3-amino-1,2,4-triazole; mDC, myeloid dendritic cell; MFI, median fluorescence intensity; MP, mononuclear phagocyte; PHPA, p-hydroxyphenyl acetic acid; TP3, TO-PRO-3.