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CCL16/LEC powerfully triggers effector and antigen‐presenting functions of macrophages and enhances T cell cytotoxicity
Author(s) -
Cappello Paola,
Caorsi Cristiana,
Bosticardo Marita,
De Angelis Stefania,
Novelli Francesco,
Forni Guido,
Giovarelli Mirella
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0403146
Subject(s) - biology , cd80 , microbiology and biotechnology , tumor necrosis factor alpha , chemokine , cd86 , cd40 , cytotoxic t cell , antigen presenting cell , macrophage , t cell , immune system , immunology , in vitro , biochemistry
The 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.