International Immunology Advance Access originally published online on June 25, 2009
International Immunology 2009 21(8):891-904; doi:10.1093/intimm/dxp056
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The CD70–CD27 interaction during the stimulation with dendritic cells promotes naive CD4+ T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humans
1 Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan
2 Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Correspondence to: N. Kadowaki; E-mail: kadowaki{at}kuhp.kyoto-u.ac.jp
CD70 expressed on dendritic cells (DCs) has been shown to play a critical role in inducing effective CD8+ T cell responses and a Th1 response in mice. However, it has not been extensively examined whether human primary DCs express CD70 and whether the CD70–CD27 interaction promotes naive CD4+ T cells to acquire the ability to produce effector cytokines during the DC–T cell interaction in humans. Here, we show that human myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells stimulated with CD40 ligand together with pro-inflammatory cytokines or Toll-like receptor ligands express CD70. Thymic stromal lymphopoietin plus prostaglandin E2 also induced CD70 on mDCs. Naive CD4+ T cells stimulated with DCs but not with anti-CD3/CD28 microbeads expressed CD70. Stimulation with CD70 together with anti-CD3/CD28 microbeads imparted the ability to produce Th1 (IFN-
), Th2 (IL-4, IL-5, IL-13) cytokines, IL-2 and tumor necrosis factor-
to naive CD4+ T cells. The production of IFN- was associated with the induction of T-bet. Naive CD4+ T cells stimulated with mDCs acquired an enhanced ability to produce a broad array of immunostimulatory cytokines in a CD70-dependent manner. These data suggest that human CD70 expressed on mDCs and activated T cells transmits a ‘basal level’ signal, rather than a ‘polarizing’ signal, to naive CD4+ T cells, in that CD70 promotes the development of CD4+ T cells that produce a variety of effector cytokines including both Th1 and Th2 types, thus contributing to the enhancement of a broad spectrum of immune responses.
Keywords: antigen-presenting cells, co-stimulation, Th1/Th2 cells
* These authors contributed equally to this study.
Transmitting editor: M. Miyasaka
Received 21 September 2008, accepted 22 May 2009.