title: In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets.
abstract: Graft-versus-host disease (GVHD) is a major obstacle in allogeneic hematopoietic cell transplantation. Given the dynamic changes in immune cell subsets and tissue organization, which occur in GVHD, localization and timing of critical immunological events in vivo may reveal basic pathogenic mechanisms. To this end, we transplanted luciferase-labeled allogeneic splenocytes and monitored tissue distribution by in vivo bioluminescence imaging. High-resolution analyses showed initial proliferation of donor CD4+ T cells followed by CD8+ T cells in secondary lymphoid organs with subsequent homing to the intestines, liver, and skin. Transplantation of purified naive T cells caused GVHD that was initiated in secondary lymphoid organs followed by target organ manifestation in gut, liver, and skin. In contrast, transplanted CD4+ effector memory T (T(EM)) cells did not proliferate in secondary lymphoid organs in vivo and despite their in vitro alloreactivity in mixed leukocyte reaction (MLR) assays did not cause acute GVHD. These findings underline the potential of T-cell subsets with defined trafficking patterns for immune reconstitution without the risk of GVHD.
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beilhack
authors.forename: Stephan
authors.initials: S
authors.lastname: Schulz
authors.forename: Jeanette
authors.initials: J
authors.lastname: Baker
authors.forename: Georg F
authors.initials: GF
authors.lastname: Beilhack
authors.forename: Courtney B
authors.initials: CB
authors.lastname: Wieland
authors.forename: Edward I
authors.initials: EI
authors.lastname: Herman
authors.forename: Enosh M
authors.initials: EM
authors.lastname: Baker
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Cao
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D008156:Luciferases; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D008156:Luciferases