title: Enhanced and aberrant T cell trafficking following total body irradiation: a gateway to graft-versus-host disease?
abstract: Pre-transplant conditioning regimens play a major role in triggering graft-versus-host disease (GVHD). This study investigated the effect of irradiation on donor T cell trafficking to lymphoid and non-lymphoid tissues by comparing the migration of carboxy-fluorescein diacetate succinimidyl ester-labelled, naïve donor T lymphocytes in vivo in irradiated and non-irradiated syngeneic mice recipients. Recruitment of adoptively transferred naïve T cells to secondary lymphoid organs was increased in irradiated mice and naïve T cells also aberrantly localized to non-lymphoid tissues. Irradiation also induced aberrant effector memory T cell migration into lymph nodes and their localization to homing-privileged non-lymphoid sites, such as the gut. The presence of a minor histocompatibility mismatch further enhanced the aberrant accumulation of T cells in both lymphoid and non-lymphoid tissue, whilst their migratory pattern was not modified as compared to fully matched irradiated recipients. These effects correlated with decreased permeability of, and the secretion of chemotactic factors by the endothelium. Our findings are consistent with the possibility that excessive, dysregulated extravasation of T cells induced by irradiation promotes the development of GVHD.
authors.affiliation: Stem Cell Biology Section, Department of Haematology, Imperial College, London, UK.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vianello
authors.forename: Laura
authors.initials: L
authors.lastname: Cannella
authors.forename: David
authors.initials: D
authors.lastname: Coe
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chai
authors.forename: Dela
authors.initials: D
authors.lastname: Golshayan
authors.forename: Federica M
authors.initials: FM
authors.lastname: Marelli-Berg
authors.forename: Francesco
authors.initials: F
authors.lastname: Dazzi
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology / Q000528:radiation effects; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology / Q000528:radiation effects; D016219:Immunotherapy, Adoptive / Q000379:methods; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D019172:Transplantation Conditioning / Q000379:methods*; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D018925:Chemokines
keywords: cellular immunology; chemokines; chemotaxis; graft-versus-host disease; transplantation