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Published online before print October 2, 2003
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Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy; and Center for Experimental Research and Medical Studies (CERMS), S. Giovanni Battista Hospital, Turin, Italy
1Correspondence: Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Ospedale San Luigi Gonzaga, 10043 Orbassano, Italy. E-mail: mirella.giovarelli{at}unito.it
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
(TNF-
) 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)-1ß, TNF-
, and IL-12. The effect of CCL16 is almost as strong as that of lipopolysaccharide and interferon-
, 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 overexpression of TNF-
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.
Key Words: tumor antigen uptake T cell priming costimulatory molecules
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