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

CD70 expressed on dendritic cells (DCs) has been shown to play a critical role in inducing effective CD8(+) T cell responses and a T(h)1 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 E-2 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 T(h)1 (IFN-gamma), T(h)2 (IL-4, IL-5, IL-13) cytokines, IL-2 and tumor necrosis factor-alpha to naive CD4(+) T cells. The production of IFN-gamma 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 T(h)1 and T(h)2 types, thus contributing to the enhancement of a broad spectrum of immune responses.