CCL16/LEC powerfully triggers effector and antigen-presenting functions of macrophages and enhances T cell cytotoxicity

Paola Cappello, Cristiana Caorsi, Marita Bosticardo, Stefania De Angelis, Francesco Novelli, Guido Forni, Mirella Giovarelli

Research output: Contribution to journalArticle

Abstract

The human CC chemokine CCL16, a liver-expressed chemokine, enhances the killing activity of mouse peritoneal macrophages by triggering their expression of tumor necrosis factor α (TNF-α) and Fas ligand. Macrophages also respond to CCL16 by enhancing their production of monocyte chemoattractant protein-1, regulated on activation, normal T cells expressed and secreted chemokines, and interleukin (IL)-β, TNF-α, and IL-12. The effect of CCL16 is almost as strong as that of lipopolysaccharide and interferon-γ, two of the best macrophage activators. Moreover, CCL16-activated macrophages overexpress membrane CD80, CD86, and CD40 costimulatory molecules and extensively phagocytose tumor cell debris. On exposure to such debris, they activate a strong, tumor-specific, cytolytic response in virgin T cells. Furthermore, cytolytic T cells generated in the presence of CCL16 display a higher cytotoxicity and activate caspase-8 in tumor target cells. This ability to activate caspase-8 depends on their over-expression of TNF-α and Fas ligand induced by CCL16. These data reveal a new function for CCL16 in the immune-response scenario. CCL16 significantly enhances the effector and the antigen-presenting function of macrophages and augments T cell lytic activity.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalJournal of Leukocyte Biology
Volume75
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • Costimulatory molecules
  • T cell priming
  • Tumor antigen uptake

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Cappello, P., Caorsi, C., Bosticardo, M., De Angelis, S., Novelli, F., Forni, G., & Giovarelli, M. (2004). CCL16/LEC powerfully triggers effector and antigen-presenting functions of macrophages and enhances T cell cytotoxicity. Journal of Leukocyte Biology, 75(1), 135-142. https://doi.org/10.1189/jlb.0403146