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.
Hashimoto-Okada
Mutsumi
M
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kitawaki
Toshio
T
Kadowaki
Norimitsu
N
Iwata
Satoshi
S
Morimoto
Chikao
C
Hori
Toshiyuki
T
Uchiyama
Takashi
T
D000818:Animals; D053282:CD27 Ligand / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D051379:Mice; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D053282:CD27 Ligand; D016207:Cytokines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7