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

• DOI: 10.1189/jlb.0403146
• Publication Date: 2003-10-07T00:16:07Z
• Authors: Paola Cappello; Cristiana Caorsi; Marita Bosticardo; Stefania De Angelis; Francesco Novelli; Guido Forni; Mirella Giovarelli
• Keywords: Rats, Inbred LEC; Cell Survival; Tumor Necrosis Factor-alpha; T-Lymphocytes; Immunology; Antigen-Presenting Cells; Cell Biology; Macrophage Activation; Interleukin-12; Recombinant Proteins; CCL16; macrophages; antigen presentations; CTL; T cell activation; Rats; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Chemokines, CC; Macrophages, Peritoneal; Immunology and Allergy; Animals; Humans; Interleukin-1; T-Lymphocytes, Cytotoxic

AbstractThe huan 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)-1β, 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 overexpression 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.