title: Immunologic resolution of human chronic graft-versus-host disease.
abstract: To determine the role of regulatory T lymphocytes (Tregs) in the pathogenesis of human chronic graft-versus-host disease (GVHD) and its clinical resolution, we evaluated long-term recipients of pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Seventy-one recipients were evaluated, 30 of whom had a history of chronic GVHD, including 16 with active chronic GVHD and 14 with resolved chronic GVHD. There were no significant clinical differences and no differences in the frequency of Tregs (CD4(+), CD127(-), CD25(+)) between the recipients with active chronic GVHD and those with resolved chronic GVHD. Using the Miyara/Sakaguchi classification scheme to identify functional Tregs, a decreased frequency of functional resting Tregs (rTregs) was identified in recipients with active chronic GVHD (P = .009 compared with normal donors; P = .001 compared with HSCT recipients without history of chronic GVHD; P = .005 compared with recipients with resolved chronic GVHD). The frequency and number of recent thymic emigrants in rTregs were normal in recipients with resolved chronic GVHD, but persistently decreased in recipients with active chronic GVHD. These results support the hypothesis that the reestablishment of normal numbers of functional rTregs is required for the clinical resolution of chronic GVHD.
authors: Division of Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Kris M
authors: KM
authors: Mahadeo
authors: Division of Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Bernadette
authors: B
authors: Masinsin
authors: Division of Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Neena
authors: N
authors: Kapoor
authors: Division of Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Ami J
authors: AJ
authors: Shah
authors: Division of Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Hisham
authors: H
authors: Abdel-Azim
authors: Division of Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: rparkman@usc.edu.
authors: Robertson
authors: R
authors: Parkman
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006402:Hematologic Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D019653:Myeloablative Agonists
keywords: Chronic graft-versus-host disease; Regulatory T lymphocytes; Thymic function