Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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(Journal of Leukocyte Biology. 2001;70:941-949.)
© 2001 by Society for Leukocyte Biology

T-cell-conditioned medium efficiently induces the maturation and function of human dendritic cells

Kazunori Kato*, Yoichi Takaue2 and Hiro Wakasugi*

* Pharmacology Division, National Cancer Center Research Institute, and
{dagger} Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

Correspondence: Kazunori Kato, Ph.D., Section Head, Pharmacology Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. E-mail: kakato{at}gan2.ncc.go.jp

We present evidence that T-cell-conditioned media (TCCM) can efficiently induce human immature dendritic cells (DC) to express high levels of immune accessory molecules commonly found on mature DC. TCCM prepared from cell-free supernatants of anti-CD3-activated T cells contained several soluble factors including CD40-ligand (sCD40L), TNF-{alpha}, and IFN-{gamma}. In contrast to moderate up-regulation of costimulatory molecules by the addition of individual cytokines or monocyte-conditioned medium, treatment of immature DC with TCCM induced a marked increase in the expression of costimulatory molecules in a dose-dependent manner. The ability of TCCM to induce such phenotypic changes could be abrogated by neutralizing antibodies specific for CD40L, TNF-{alpha}, and IFN-{gamma}, indicating that these factors present in TCCM are mainly implicated in the maturation of DC. Importantly, TCCM-treated DC can produce significantly higher levels of IL-12 and are highly effective stimulators in allogenenic and autologous mixed-lymphocyte reactions. Overall, these findings show that cultivation with TCCM is an efficient approach for the induction of mature DC that should be useful in eliciting antigen-specific immune responses against cancer and viruses.

Key Words: antigen presentation • costimulatory molecules • T lymphocytes • cellular activation




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