CD40-CD40 ligand interactions in vivo regulate migration of antigen-bearing dendritic cells from the skin to draining lymph nodes.
Whereas CD40-CD40 ligand interactions are important for various dendritic cell (DC) functions in vitro, their in vivo relevance is unknown. We analyzed the DC status of CD40 ligand -/- mice using a contact hypersensitivity (CHS) model system that enables multiple functions of DCs to be assessed in vivo. Immunohistochemistry of skin sections revealed no differences in terms of numbers and morphology of dendritic epidermal Langerhans cells (LCs) in unsensitized CD40 ligand -/- mice as compared with wild-type C57BL/6 mice. However, after contact sensitization of CD40 ligand -/- mice, LCs failed to migrate out of the skin and substantially fewer DCs accumulated in draining lymph nodes (DLNs). Furthermore, very few antigen-bearing DCs could be detected in the paracortical region of lymph nodes draining sensitized skin. This defect in DC migration after hapten sensitization was associated with defective CHS responses and decreased cutaneous tumor necrosis factor (TNF)-alpha production and was corrected by injecting recombinant TNF-alpha or an agonistic anti-CD40 monoclonal antibody. Thus, CD40-CD40 ligand interactions in vivo regulate the migration of antigen-bearing DCs from the skin to DLNs via TNF-alpha production and play a vital role in the initiation of acquired T cell-mediated immunity.
Moodycliffe
A M
AM
Department of Immunology-178, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Shreedhar
V
V
Ullrich
S E
SE
Walterscheid
J
J
Bucana
C
C
Kripke
M L
ML
Flores-Romo
L
L
D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology*; D003877:Dermatitis, Contact; D004195:Disease Models, Animal; D007801:Langerhans Cells / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D008198:Lymph Nodes; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand