title: Severe chronic graft-versus-host disease is characterized by a preponderance of CD4(+) effector memory cells relative to central memory cells.
abstract: Donor alloreactive CD4(+) T cells are important to the pathogenesis of chronic graft-versus-host disease (cGVHD), but specific subsets of CD4(+) T cells responsible for GVHD have not been defined. We hypothesized that cGVHD might be associated with a preponderance of CD4(+) effector memory cells (CCR7(-)/CD62L(low), CD4(EM)). We analyzed CCR7 and CD62L expression on CD4(+) T cells from stem cell transplantation patients, who did or did not develop cGVHD, and healthy donors. Patients with cGVHD had a higher percentage of CD4(EM) cells (35.5% +/- 2.9%) than healthy donors (13.8% +/- 0.7%; P <.0001) or patients without cGVHD that received a transplant (21.7% +/- 2.1%; P <.01). Using corticosteroid dose as a surrogate marker for cGVHD severity, severe cGVHD was associated with a higher percentage of CD4(EM) cells. The proportion of CD4(EM) cells in corticosteroid-dependent patients with systemic lupus erythematosis or Wegener granulomatosis did not differ from patients without cGVHD that received a transplant. This finding implies that overrepresentation of CD4(EM) cells is a unique feature of cGVHD.
authors.affiliation: Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892-1886, USA. kyamashita@niaid.nih.gov
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamashita
authors.forename: Uimook
authors.initials: U
authors.lastname: Choi
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Woltz
authors.forename: Susan F
authors.initials: SF
authors.lastname: Foster
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sneller
authors.forename: Francis T
authors.initials: FT
authors.lastname: Hakim
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bishop
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.forename: Marisa
authors.initials: M
authors.lastname: Tamari
authors.forename: Kathleen
authors.initials: K
authors.lastname: Castro
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
authors.forename: Susan F
authors.initials: SF
authors.lastname: Leitman
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002908:Chronic Disease; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D019041:L-Selectin / Q000032:analysis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin