Résumé
Dendritic cells (DC) are as master regulators of the adaptive immune response, providing both cognate antigen and costimulation required for T cell activation as well as cytokines (e.g., IL-12, TNF, and IL-6) that drive T cell expansion and differentiation. While the role of DCs in T cell activation is well known, here we show that DCs play an unexpected role in shaping the T cell repertoire within inflamed lymph nodes (LN) by promoting trafficking across vascular gateways termed high endothelial venules (HEV). Immunization of mice with bone marrow-derived DCs matured ex vivo by TLR4 and 9 agonists (LPS and ODN-CpG, respectively), but not a TLR2 agonist (Pam3CSK4), increased the intravascular density of two hallmark adhesion molecules, peripheral lymph node addressin (PNAd) and intercellular adhesion molecule-1 (ICAM-1), selectively in HEVs of inflamed LNs. Increased PNAd and ICAM-1 display occurred rapidly after immunization (within 12 h) and coincided with improved trafficking of naïve and central memory T cells as well as increased LN size. PNAd and ICAM-1 expression reverted to homeostatic levels 24-48 h post immunization. Remarkably, increased adhesion molecule expression was abrogated by loss of a single cytokine, IL-6, from immunizing DCs. These findings suggest a model whereby IL-6-producing DC actively promote trafficking in HEVs, thereby increasing the probability that naïve T cells come into contact with cognate antigen-loaded DCs in inflamed LN.