title: Aggregation of antigen-specific T cells at the inoculation site of mature dendritic cells.
abstract: Cellular immune responses are initiated by direct interaction of naive T cells with professional antigen-presenting cells, i.e., dendritic cells. In general, this interaction takes place in secondary lymphoid organs to which both naive T cells and mature dendritic cells preferentially home. This physiologic scenario differs substantially, however, from therapeutic dendritic-cell-based vaccinations used to treat human cancer. In fact, only a small fraction of intradermally injected dendritic cells migrate to the draining lymph node and the majority of cells remain at the site of inoculation. These sites are characterized by a distinct oligoclonal T cell infiltrate comprising both L-Selectin+/CD45RA+ and L-Selectin+/CD45RA- cells. Blood vessels expressing peripheral lymph node addressin represent possible entry channels for such naive and central memory T cells, the former probably attracted by dendritic cell-CK1 produced by the injected dendritic cells. In situ staining with multimeric peptide/major histocompatibility complex class I complexes revealed that infiltrating T cells specifically recognize peptide epitopes presented by the injected dendritic cells. Thus, the fraction of dendritic cells not migrating to secondary lymphatic tissue after therapeutic inoculation nevertheless seem to be involved in a specific immune modulation.
authors.affiliation: Department of Dermatology, Julius Maximilians University, Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.forename: Lars Østergaard
authors.initials: LØ
authors.lastname: Pedersen
authors.forename: Petra
authors.initials: P
authors.lastname: Keikavoussi
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.forename: Per thor
authors.initials: Pt
authors.lastname: Straten Pt
authors.forename: Eva-Bettina
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Eckhart
authors.initials: E
authors.lastname: Kämpgen
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology*; D002999:Clone Cells; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D020405:Dermis / Q000166:cytology / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D019041:L-Selectin / Q000032:analysis; D008297:Male; D008545:Melanoma / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012878:Skin Neoplasms / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D019041:L-Selectin