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Medientyp:
E-Artikel
Titel:
Effective Collaboration between Marginal Metallophilic Macrophages and CD8⁺ Dendritic Cells in the Generation of Cytotoxic T Cells
Beteiligte:
Backer, Ronald;
Schwandt, Timo;
Greuter, Mascha;
Oosting, Marije;
Jüngerkes, Frank;
Tüting, Thomas;
Boon, Louis;
O'Toole, Tom;
Kraal, Georg;
Limmer, Andreas;
den Haan, Joke M. M.;
Bevan, Michael J.
Erschienen:
National Academy of Sciences, 2010
Erschienen in:
Proceedings of the National Academy of Sciences of the United States of America, 107 (2010) 1, Seite 216-221
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
The spleen is the lymphoid organ that induces immune responses toward blood-borne pathogens. Specialized macrophages in the splenic marginal zone are strategically positioned to phagocytose pathogens and cell debris, but are not known to play a role in the activation of T-cell responses. Here we demonstrate that splenic marginal metallophilic macrophages (MMM) are essential for crosspresentation of blood-borne antigens by splenic dendritic cells (DCs). Our data demonstrate that antigens targeted to M MM as well as blood-borne adenoviruses are efficiently captured by MMM and exclusively transferred to splenic CD8⁺ DCs for cross-presentation and for the activation of cytotoxic Ô lymphocytes. Depletion of macrophages in the marginal zone prevents cytotoxic T lymphocyte activation by CD8⁺ DCs after antibody targeting or adenovirus infection. Moreover, we show that tumor antigen targeting to MMM is very effective as antitumor immunotherapy. Our studies point to an important role for splenic MMM in the initial steps of CD8⁺ T-cell immunity by capturing and concentrating blood-borne antigens and the transfer to cross-presenting DCs which can be used to design vaccination strategies to induce antitumor cytotoxic T-cell immunity.