Article
Mucosal Immunology (2008) 1, 38–48; doi:10.1038/mi.2007.4
Retinoic acid receptor signaling levels and antigen dose regulate gut homing receptor expression on CD8+ T cells
M Svensson1, B Johansson-Lindbom1, F Zapata1, E Jaensson1, L M Austenaa2, R Blomhoff2 and W W Agace1
- 1Section for Immunology, Lund University, Lund, Sweden
- 2Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Correspondence: WW Agace, (william.agace@med.lu.se)
Received 16 July 2007; Accepted 24 August 2007.
Abstract
Recent studies have highlighted a central role for intestinal dendritic cells (DCs) and vitamin A metabolite retinoic acid (RA) in the generation of 
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7+ CCR9+"gut tropic" effector T cells. Here, using RA-responsive element reporter mice, we demonstrate that both splenic and mesenteric lymph node (MLN) DCs enhanced retinoic acid receptor (RAR) signaling in CD8+ T cells; however, only a subset of MLN DCs, expressing the integrin -chain CD103, induced an early RAR signal that is required for efficient CCR9 induction. MLN-primed CD8+ T cells also received enhanced RAR-dependent signals compared with splenic-primed CD8+ T cells in vivo. Further DC-mediated induction of gut homing receptors was inhibited at a high antigen dose without influencing RAR signaling events, and resulted in less efficient CD8+ T-cell entry into the small intestinal mucosa. These results highlight a complex interplay between antigen dose and DC subset-induced RAR signaling events in the generation of tissue tropic effector T-cell subsets.
