title: An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues.
abstract: Transfer of T cells to freshly irradiated allogeneic recipients leads to their rapid recruitment to nonlymphoid tissues, where they induce graft-versus-host disease (GVHD). In contrast, when donor T cells are transferred to established mixed chimeras (MCs), GVHD is not induced despite a robust graft-versus-host (GVH) reaction that eliminates normal and malignant host hematopoietic cells. We demonstrate here that donor GVH-reactive T cells transferred to MCs or freshly irradiated mice undergo similar expansion and activation, with similar up-regulation of homing molecules required for entry to nonlymphoid tissues. Using dynamic two-photon in vivo microscopy, we show that these activated T cells do not enter GVHD target tissues in established MCs, contrary to the dogma that activated T cells inevitably traffic to nonlymphoid tissues. Instead, we show that the presence of inflammation within a nonlymphoid tissue is a prerequisite for the trafficking of activated T cells to that site. Our studies help to explain the paradox whereby GVH-reactive T cells can mediate graft-versus-leukemia responses without inducing GVHD in established MCs.
authors.affiliation: Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.forename: Daniel
authors.initials: D
authors.lastname: Côté
authors.forename: Jennifer
authors.initials: J
authors.lastname: Buchli
authors.forename: Pete
authors.initials: P
authors.lastname: Cotter
authors.forename: Richard
authors.initials: R
authors.lastname: Hsu
authors.forename: Guiling
authors.initials: G
authors.lastname: Zhao
authors.forename: Teviah
authors.initials: T
authors.lastname: Sachs
authors.forename: Costas M
authors.initials: CM
authors.lastname: Pitsillides
authors.forename: Roderick
authors.initials: R
authors.lastname: Bronson
authors.forename: Terry
authors.initials: T
authors.lastname: Means
authors.forename: Charles
authors.initials: C
authors.lastname: Lin
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006087:Graft vs Host Reaction / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D011828:Radiation Chimera / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D051193:Toll-Like Receptors