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(Journal of Leukocyte Biology. 2000;68:111-118.)
© 2000 by Society for Leukocyte Biology

Vascular endothelial cells provide T cells with costimulatory signals via the OX40/gp34 system

Akane Kunitomi^*, Toshiyuki Hori^*, Akihiro Imura and Takashi Uchiyama^*

^* Department of Hematology/Oncology and
Department of Tumor Biology, Graduate School of Medicine, Kyoto University, Japan

Correspondence: Toshiyuki Hori, MD, Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-kawaracho, Sakyo, Kyoto, 606-8507, Japan. E-mail: thori{at}kuhp.kyoto-u.ac.jp

We investigated whether gp34, the ligand of OX40, expressed on EC is involved in costimulation of T cells. Normal CD4⁺ T cells were stimulated with anti-CD3-coated beads, phytohemagglutinin (PHA), or concanavalin A (Con A) in the presence or absence of irradiated human umbilical vein endothelial cells (HUVEC). Stimulation of T cells with each of these mitogens results in significant T-cell proliferation only when HUVEC were present, and this proliferation was inhibited markedly by anti-OX40 or anti-gp34 monoclonal antibody (mAb). T cells cultured with HUVEC produced more interleukin (IL)-2 than those cultured without HUVEC. The addition of anti-IL-2R chain and anti-IL-2R ß chain mAbs abolished the costimulatory effects of HUVEC. Thus, the augmentation of T-cell proliferation appears to be attributable to increased IL-2 production. These results suggest that gp34 expressed on HUVEC plays a role in potentiation of T-cell immune response by providing OX40⁺ T cells with costimulatory signals.

Key Words: endothelial biology • T lymphocytes • costimulation • TNF receptor family

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