TY - JOUR
T1 - Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo
AU - Montfoort, Nadine
AU - Mangsbo, SM
AU - Camps, MGM
AU - van Maren, WWC
AU - Verhaart, IEC
AU - Waisman, A
AU - Drijfhout, JW
AU - Melief, CJM
AU - Verbeek, JS
AU - Ossendorp, F
PY - 2012
Y1 - 2012
N2 - 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 na?ve 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.
AB - 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 na?ve 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.
U2 - 10.1002/eji.201141613
DO - 10.1002/eji.201141613
M3 - Article
C2 - 22488363
SN - 0014-2980
VL - 42
SP - 598
EP - 606
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -