Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo
2012 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 42, no 3, 598-606 p.Article in journal (Refereed) Published
Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross-presentation of antigen to CD8+ T cells. Mice with hapten-specific circulating antibodies, but naϊve for the T-cell antigen, were infused with haptenated antigen and CD8+ T-cell induction was measured. Mice with circulating hapten-specific antibodies showed significantly enhanced cross-presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross-presentation in mice with circulating antigen-specific antibodies was associated with improved antigen capture by APCs. Importantly, CD11c+ APCs were responsible for the enhanced and sustained cross-presentation, although CD11c− APCs had initially captured a significant amount of the injected antigen. Thus, in vivo formation of antigen-antibody immune complexes improves MHC class I cross-presentation, and CD8+ T-cell activation, demonstrating that humoral immunity can aid the initiation of systemic cellular immunity. These findings have important implications for the understanding of the action of therapeutic antibodies against tumor-associated antigens intensively used in the clinic nowadays.
Place, publisher, year, edition, pages
2012. Vol. 42, no 3, 598-606 p.
Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-187543DOI: 10.1002/eji.201141613PubMedID: 22488363OAI: oai:DiVA.org:uu-187543DiVA: diva2:575101
De 2 första författarna delar förstaförfattarskapet.2012-12-072012-12-072015-03-01