Enhancement of tumoricidal activity of alveolar macrophages via CD40- CD40 ligand interaction

Kazuyoshi Imaizumi, Tsutomu Kawabe, Satoshi Ichiyama, Hitoshi Kikutani, Hideo Yagita, Kaoru Shimokata, Yoshinori Hasegawa

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29 Citations (Scopus)

Abstract

CD40-CD40 ligand (CD40L) interaction was originally defined as important molecules for the development of humoral immunity. Thereafter, some investigations have focused on its essential roles for the induction of cell- mediated immunity in host defenses. Here we investigated the antitumor activity of murine alveolar macrophages through CD40-CD40L interaction. The CD40L gene was transfected into murine lung cancer cells (3LLSA), and CD40L- expressing clones (3LLSA-CD40L) were established. Stimulation of CD40 molecules on the surface of alveolar macrophages with 3LLSA-CD40L cells induced the production of nitric oxide, tumor necrosis factor-α, and interleukin-12 and the tumoricidal activity of alveolar macrophages in the presence of interferon-γ, which increased the surface expression of CD40 molecules on alveolar macrophages. These findings were not observed when alveolar macrophages were obtained from CD40-deficient mice. On the other hand, interleukin-6 production by alveolar macrophages did not depend on CD40-CD40L interaction. We also established a murine melanoma cell line expressing CD40L (B16 4A5-CD40L) that could induce tumoricidal activity of alveolar macrophages. Furthermore, when spleen cells were cocultivated with 3LLSA-CD40L cells, specific cytotoxic T lymphocytes for wild-type 3LLSA cells could be induced. These results suggest that CD40L gene transfer into tumor cells may induce antitumor immunity in a tumor-bearing host and may offer a new strategy for cancer gene therapy.

Original languageEnglish
Pages (from-to)L49-L57
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume277
Issue number1 21-1
DOIs
Publication statusPublished - 07-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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