Impaired CD40-signalling in Langerhans' cells from murine neonatal draining lymph nodes: implications for neonatally induced cutaneous tolerance.
Cutaneous tolerance to antigens may be induced in mice through application of antigen during the first few days following birth. The mechanism governing this neonatally induced tolerance remains uncertain. We employed a contact hypersensitivity model to analyse dendritic cell (DC) function and the expression of classical and non-classical lymphocyte populations within the neonate. Examination of draining lymph node DC after antigenic challenge of the skin revealed these DC to be significantly deficient in their ability to stimulate antigen-specific T cell proliferation. Co-stimulatory molecule (CD40, CD80 and CD86) expression of these cells was deficient in comparison to adult DC, and functional tests revealed these cells to possess a critical absence of CD40 signalling. A numerical analysis of classical and non-classical lymphocyte expression demonstrated that while the neonatal spleen is devoid of T cells, the lymph nodes have a normal repertoire of T, B, gammadelta and CD4+CD25+ lymphocytes but an increased expression of natural killer (NK) cells. This study indicates that functionally deficient DC are likely contributors to neonatally induced cutaneous tolerance.
Simpson
C C
CC
Division of Pathology, University of Tasmania, Hobart, Tasmania, Australia. csimpson@utas.edu.au
Woods
G M
GM
Muller
H K
HK
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis*; D003877:Dermatitis, Contact / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins