Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation.
Activation of dendritic cells (DCs) enhances their ability to prime naïve T cells. How activation renders them immunogenic rather than tolerogenic is unclear. Here, we show, using temporally regulated expression of a transgene-encoded neoself antigen in DCs, that either prolonged antigen presentation or DC activation could elicit full expansion, effector cytokine production, and memory-cell differentiation. Microarray analysis of gene expression in T cells showed that all changes linked to DC activation through CD40 could be reproduced by persistent antigen delivery, suggesting that stabilization of antigen presentation is an important consequence of DC activation in vivo. In this system, DC activation by CD40 engagement indeed extended their ability to present antigen to CD4(+) T cells in vivo, although different results were obtained with antigen delivered to DCs by means of endocytosis from the cell surface. These results suggest that antigen persistence may be an important discriminator of immunogenic and tolerogenic antigen exposure.
Obst
Reinhard
R
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
van Santen
Hisse-Martien
HM
Melamed
Rachel
R
Kamphorst
Alice O
AO
Benoist
Christophe
C
Mathis
Diane
D
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D007107:Immune System; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000941:Antigens; D016207:Cytokines