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

Journal of Leukocyte Biology

Francesco Novelli¹  Mirella Giovarelli¹  Cristiana Caorsi¹  Guido Forni¹  Paola Cappello¹  Marita Bosticardo¹  Stefania De Angelis¹ 

[1] 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 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 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

关键词: tumor antigen uptake;    T cell priming;    costimulatory molecules;   

DOI  :  10.1189/jlb.0403146

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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)-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.

【 授权许可】

Unknown