title: Blood and gastric FOXP3+ T cells are not decreased in human gastric graft-versus-host disease.
abstract: Previous studies suggest regulatory T cells (Tregs) inhibit graft-versus-host disease (GVHD) in mouse and human hematopoietic cell transplant (HCT) recipients. As the gastrointestinal tract represents one of the most common and severe sites of GVHD-related tissue damage, we sought to determine whether a deficit in circulating or gastric mucosal Treg numbers correlates with the clinical onset of gastric GVHD. We used the marker FOXP3 to quantify Tregs in blood and in gastric antral biopsies in a cohort of 60 allogeneic HCT recipients undergoing endoscopy at a single center to evaluate symptoms suspicious for gastrointestinal GVHD. We show for the first time in the gastric mucosa and, contrary to existing reports, in the blood, that the percent of T cells expressing FOXP3 is at least as high in the presence as in the absence of GVHD involving the upper gut. There was no correlation of Treg frequency with the histologic or clinical severity of gastrointestinal GVHD. We conclude that Treg depletion is not a central feature in the pathogenesis of gastric GVHD in humans.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, WA 98101, USA. jdlord@u.washington.edu
authors.forename: James D
authors.initials: JD
authors.lastname: Lord
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hackman
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Moklebust
authors.forename: David M
authors.initials: DM
authors.lastname: Hockenbery
authors.forename: Gideon
authors.initials: G
authors.lastname: Steinbach
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: George B
authors.initials: GB
authors.lastname: McDonald
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D015331:Cohort Studies; D005260:Female; D051858:Forkhead Transcription Factors; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006086:Graft vs Host Disease / Q000097:blood* / Q000276:immunology; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011706:Pyloric Antrum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013272:Stomach Diseases / Q000097:blood* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors