Optimal stimulation for CD70 induction on human monocyte-derived dendritic cells and the importance of CD70 in naive CD4+ T-cell differentiation
Article first published online: 26 FEB 2010
© 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd
Volume 130, Issue 1, pages 137–149, May 2010
How to Cite
Arimoto-Miyamoto, K., Kadowaki, N., Kitawaki, T., Iwata, S., Morimoto, C. and Uchiyama, T. (2010), Optimal stimulation for CD70 induction on human monocyte-derived dendritic cells and the importance of CD70 in naive CD4+ T-cell differentiation. Immunology, 130: 137–149. doi: 10.1111/j.1365-2567.2010.03220.x
- Issue published online: 6 APR 2010
- Article first published online: 26 FEB 2010
- Received 28 July 2009; revised 12 November 2009; accepted 18 November 2009.
- dendritic cells;
- T cells
Studies in mice have shown that CD70 on dendritic cells (DCs) is sufficient to convert T-cell tolerance into immunity and hence induce anti-tumour immune responses. Therefore, it is important to investigate (i) optimal stimuli to induce CD70 on human monocyte-derived DCs (MoDCs), which are widely used for tumour immunotherapy, and (ii) the role of CD70 in functional differentiation of naive CD4+ and CD8+ T cells stimulated with MoDCs. We show that interferon-α (IFN-α) is a key cytokine to differentiate monocytes into DCs with the capacity to express CD70 upon maturation. CD70 expression on IFN-α-induced MoDCs was elicited by different categories of maturation-inducing factors (Toll-like receptor ligands, CD40 ligand and pro-inflammatory mediators), among which prostaglandin E2 was most effective. Naive T cells stimulated with MoDCs also expressed CD70. Stimulation with MoDCs promoted naive CD4+ T cells to acquire the ability to produce T helper type 1 and 2 cytokines in a CD70-dependent manner. In contrast, the CD70–CD27 interaction diminished the production of an immunoregulatory cytokine IL-10. The CD27 signal did not play a dominant role in the induction of effector molecules in naive CD8+ T cells during the stimulation with MoDCs. This study adds a novel function to the versatile cytokines, type I IFNs, that is, the induction of CD70 on MoDCs. CD70 promotes naive CD4+ T cells to acquire immunostimulatory activity through the DC–T-cell and T-cell–T-cell interactions during the stimulation with MoDCs. Hence, the CD70–CD27 interaction may play an important role in inducing effective immune responses in DC-based immunotherapy.