Activated NKT cells increase dendritic cell migration and enhance CD8+ T cell responses in the skin.
Activated NKT cells produce cytokines such as IL-4 and IFN-gamma that function locally to influence the strength and functional development of antigen-specific T cells. Here we identify an alternative mechanism by which NKT cells influence the strength of T cell responses: through modulation of peripheral dendritic cell (DC) trafficking. NKT cell activation with alpha-galactosylceramide induced high systemic levels of TNF-alpha that mediated increased DC migration from skin to draining lymph nodes. This increased DC trafficking led to a threefold increase in effector T cell priming and in the immune response elicited to antigen challenge when alpha-galactosylceramide was given at the time of immunization of the skin. These studies provide important implications for the use of NKT cell activation strategies to manipulate T cell-mediated responses including responses to cutaneous tumors and graft vs. host disease.
Gorbachev
Anton V
AV
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195-0001, USA. gorbaca@ccf.org
Fairchild
Robert L
RL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012867:Skin / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D005699:Galactosylceramides; D014409:Tumor Necrosis Factor-alpha; C493154:alpha-galactosylceramide