title: Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells.
abstract: Chronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and peripheral mechanisms. Defective thymic function may contribute to dysregulation of central tolerance, but few studies have addressed peripheral tolerance. Recently a population of CD4+CD25+ T cells (Treg cells) has been characterized, which controls immunologic reactivity in vivo and which on transfer can prevent experimental acute GVHD. We investigated the number and function of peripheral blood CD4+CD25high T cells in patients more than 100 days after allogeneic hematopoietic stem cell transplantation. Patients with cGVHD had markedly elevated numbers of CD4+CD25high T cells as compared to patients without GVHD. CD4+CD25high T cells derived from patients in both groups were of donor origin, lacked markers of recent activation, and expressed intracellular CD152. In contrast to controls, CD4+CD25high T cells derived from patients with cGVHD were characterized by lower surface CD62L expression. In vitro, CD4+CD25high T cells were hyporesponsive to polyclonal stimulation and suppressed the proliferation and cytokine synthesis of CD4+CD25- cells, an effect that was independent of interleukin 10. These results indicate that chronic graft-versus-host injury does not occur as a result of Treg cell deficiency.
authors: Department of hematology, Institute of Cancer Studies, University of Birmingham, Edgbaston, United Kingdom.
authors: Fiona J
authors: FJ
authors: Clark
authors: Richard
authors: R
authors: Gregg
authors: Karen
authors: K
authors: Piper
authors: Debbie
authors: D
authors: Dunnion
authors: Lisa
authors: L
authors: Freeman
authors: Mike
authors: M
authors: Griffiths
authors: Gulnaz
authors: G
authors: Begum
authors: Premini
authors: P
authors: Mahendra
authors: Charles
authors: C
authors: Craddock
authors: Paul
authors: P
authors: Moss
authors: Ronjon
authors: R
authors: Chakraverty
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016130:Immunophenotyping; D019041:L-Selectin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014019:Tissue Donors
chemical_list: D015375:Receptors, Interleukin-2; D019041:L-Selectin