Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state.
TCR transgenic mice that express a peptide antigen in keratinocytes develop a lethal CD8 T cell-dependent autoimmune disease. We employed an adoptive transfer system to understand this disease and show that transfer of low numbers of naive CD8 T cells into peptide transgenic mice caused chronic skin disease. The antigen-presenting cell that initiated this response was the epidermal Langerhans cell. Naive CD8 T cells proliferated extensively, migrated to tissues, developed effector function, and were capable of making a recall response. These features are very different from the abortive activation of CD8 T cells that occurred in response to the same antigen presented by APC from other tissues. Furthermore, tolerance was dominant when the antigen was presented by both Langerhans cells and other APC. These data suggest that Langerhans cells do not have tolerogenic properties in the steady state.
Mayerova
Dita
D
Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, 312 Church Street SE, Minneapolis 55455, USA.
Parke
Evan A
EA
Bursch
Laura S
LS
Odumade
Oludare A
OA
Hogquist
Kristin A
KA
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D053547:Keratin-14; D007633:Keratins / Q000235:genetics; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D012871:Skin Diseases / Q000276:immunology
D001324:Autoantigens; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; D007633:Keratins; D010047:Ovalbumin