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* Tenovus Research Laboratory, Cancer Sciences Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom; and
Edward Jenner Institute for Vaccine Research, Compton, Newbury, United Kingdom
Dendritic cell (DC) conditioning by CD4+ T cells, or via engagement of innate receptors, is thought to be essential for CD8+ T cell priming. However, the molecular features that distinguish a conditioned DC from an unconditioned DC are poorly defined. In this study, we investigate the role of CD70, a member of the TNF superfamily that is expressed on activated DC, in CD4+ Th-dependent and -independent CD8+ T cell responses. We demonstrate that CD70 is required for CD4+ T cell-dependent priming of CD8+ T cells as well as priming mediated by the viral signature, dsRNA. Accordingly, mice that were subjected to CD70 blockade during the primary response fail to generate a memory CD8+ T cell response. Furthermore, we find that CD70 is dispensable for CD4+ T cell expansion and help for B cells, thus suggesting a direct role for CD70 in CD8+ T cell priming. Our results show that the innate and adaptive (CD4+ T cells) arms of the immune system use a common signaling pathway in driving CD8+ T cell responses and suggest that expression of CD70 on DC represents the hallmark of conditioned DC.
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 work was funded by Tenovus.
2 Address correspondence and reprint requests to Dr. Aymen Al-Shamkhani, Tenovus Research Laboratory, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K. E-mail address: aymen{at}soton.ac.uk
3 Abbreviations used in this paper: DC, dendritic cell; BM, bone marrow; PAMP, pathogen-associated molecular pattern; poly(I:C), polyinosinic-polycytidylic acid.
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