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Triggering of Dendritic Cell Responses after Exposure to Activated, but Not Resting, Apoptotic PBMCs¹

Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

Dendritic cells (DCs) can be activated by signaling via pathogen receptors, by interaction with activated T cells or by exposure to inflammatory mediators. Clearance of apoptotic cells by DCs is generally considered a silent event that is not associated with an inflammatory response. Necrotic cell death, in contrast, leads to induction of inflammation. However, emerging data challenge the view of apoptotic cells as inherently nonimmunogenic. In this study, we report that the activation state of the apoptotic cell may determine whether the exposed DC becomes activated and rendered proficient in Ag presentation. We show that coculture with activated, but not resting, apoptotic PBMCs leads to up-regulation of surface expression of the costimulatory molecules CD80, CD83, and CD86 in human DCs as well as release of proinflammatory cytokines. Furthermore, we show that DCs exposed to allogeneic, activated apoptotic PBMCs induce proliferation and IFN- production in autologous T cells. Together, these findings show that activated apoptotic PBMCs per se provide an activation/maturation signal to DCs, suggesting that activated apoptotic PBMCs possess endogenous adjuvant properties.

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 research was supported by the Swedish Research Council, Swedish Cancer Society, Swedish International Development Cooperation Agency/Department for Research Cooperation, Swedish Physicians Against AIDS Research Foundation, European Commission STREP-018953, and Swedish Foundation for Strategic Research.

² Address correspondence and reprint requests to Dr. Ulrika Johansson, Department of Medicine, Center for Infectious Medicine, F59, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. E-mail address: ulrika.johansson{at}ki.se

³ Abbreviations used in this paper: DC, dendritic cell; PI, propidium iodide; SEB, staphylococcal enterotoxin B; CD40L, CD40 ligand; ac, apoptotic cell; nc, necrotic cell; o.n., overnight.