title: The central nervous system is a target of acute graft versus host disease in mice.
abstract: Despite significant advances in prevention and management, graft versus host disease (GVHD) is still a leading complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although skin, gut, liver, thymus, and lung are GVHD targets, neurological complications (NC) have also been reported following allo-HSCT. We demonstrate that the central nervous system (CNS) can be a direct target of alloreactive T cells following allo-HSCT in mice. We found significant infiltration of the CNS with donor T lymphocytes and cell death of neurons and neuroglia in allo-HSCT recipients with GVHD. We also found that allo-HSCT recipients with GVHD had deficits in spatial learning/memory and demonstrated increased anxious behavior. These findings highlight CNS sensitivity to damage caused by alloreactive donor T cells and represent the first characterization of target cell subsets and NC during GVHD. Therefore, these clinically relevant studies offer a novel and rational explanation for the well-described neurological symptoms observed after allo-HSCT.
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. vandenbm@mskcc.org
authors.forename: Steffen
authors.initials: S
authors.lastname: Hartrampf
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Dudakov
authors.forename: Linda K
authors.initials: LK
authors.lastname: Johnson
authors.forename: Odette M
authors.initials: OM
authors.lastname: Smith
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tsai
authors.forename: Natalie V
authors.initials: NV
authors.lastname: Singer
authors.forename: Mallory L
authors.initials: ML
authors.lastname: West
authors.forename: Alan M
authors.initials: AM
authors.lastname: Hanash
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.forename: Bingfang
authors.initials: B
authors.lastname: Liu
authors.forename: Miklos
authors.initials: M
authors.lastname: Toth
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000473:pathology; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000150:complications*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications; D013601:T-Lymphocytes / Q000473:pathology*; D014184:Transplantation, Homologous