title: Intravenous infusion of syngeneic apoptotic cells by photopheresis induces antigen-specific regulatory T cells.
abstract: The basis of extracorporeal photopheresis is the reinfusion of leukocytes previously exposed to 8-methoxypsoralen (8-MOP) and UVA radiation. It has been approved for the palliative treatment of cutaneous T cell lymphoma and has reported benefits in autoimmune diseases, transplant rejection, and graft-vs-host disease. However, the underlying mechanism of photopheresis remains unresolved. Because UVB radiation can cause immune tolerance via induction of regulatory T cells, we studied whether photopheresis exerts a similar effect extracorporeally. Therefore, we established a model of photopheresis using a murine model of contact hypersensitivity. Splenocytes and lymph node cells of mice that were sensitized with dinitrofluorobenzene were exposed to 8-MOP plus UVA in vitro. Intravenous injection of these cells into naive mice caused inhibition of a hapten immune response, which was lost upon depletion of CD11c(+) cells but not T cells. Mice that received untreated cells or cells exposed to UVA or 8-MOP alone were not affected. Inhibition was cell-mediated and Ag-specific as demonstrated by transfer of tolerance from the primary recipients into naive animals, which could, however, properly respond to the unrelated hapten oxazolone. Transfer activity was lost when cells were depleted of CD4(+) or CD25(+) subpopulations. These data suggest that photopheresis exerts its immunomodulatory effects via the induction of Ag-specific regulatory T cells.
authors.affiliation: Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University Münster, Münster, Germany.
authors.forename: Akira
authors.initials: A
authors.lastname: Maeda
authors.forename: Agatha
authors.initials: A
authors.lastname: Schwarz
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kernebeck
authors.forename: Nicole
authors.initials: N
authors.lastname: Gross
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aragane
authors.forename: David
authors.initials: D
authors.lastname: Peritt
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D039521:CD11c Antigen / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000276:immunology / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology; D007262:Infusions, Intravenous; D017708:Leukocyte Transfusion; D008099:Liver / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D008213:Lymphocyte Activation / Q000235:genetics / Q000528:radiation effects; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D017893:Photopheresis / Q000379:methods; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000528:radiation effects; D014185:Transplantation, Isogeneic
chemical_list: D039521:CD11c Antigen; D018984:Epitopes, T-Lymphocyte; D006241:Haptens