title: Peripheral T cells re-enter the thymus and interfere with central tolerance induction.
abstract: The thymus mainly contains developing thymocytes that undergo thymic selection. In addition, some mature activated peripheral T cells can re-enter the thymus. We demonstrated in this study that adoptively transferred syngeneic Ag-specific T cells can enter the thymus of lymphopenic mice, where they delete thymic dendritic cells and medullary thymic epithelial cells in an Ag-specific fashion, without altering general thymic functions. This induced sustained thymic release of autoreactive self-Ag-specific T cells suggested that adoptively transferred activated T cells can specifically alter the endogenous T cell repertoire by erasing negative selection of their own specificities. Especially in clinical settings in which adoptively transferred T cells cause graft-versus-host disease or graft-versus-leukemia, as well as in adoptive tumor therapies, these findings might be of importance, because the endogenous T cell repertoire might be skewed to contribute to both manifestations.
authors.affiliation: Institute for Immunology, Ludwig-Maximilians-University, D-80336 Munich, Germany.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Edelmann
authors.forename: Peggy
authors.initials: P
authors.lastname: Marconi
authors.forename: Thomas
authors.initials: T
authors.lastname: Brocker
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D002678:Chimera; D003713:Dendritic Cells / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D008213:Lymphocyte Activation; D008231:Lymphopenia; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D017634:Self Tolerance / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology