title: Unique abnormalities of CD4(+) and CD8(+) central memory cells associated with chronic graft-versus-host disease improve after extracorporeal photopheresis.
abstract: Chronic graft-versus-host disease (cGVHD) remains a problematic complication of allogeneic hematopoietic stem cell transplantation. Laboratory parameters correlated with cGVHD have not been fully defined, although changes in CD4/CD8 ratios occur and a decrease in CD4(+) central memory T cells has been noted. Extracorporeal photopheresis (ECP) is an effective therapy for steroid-refractory cGVHD. We have noted changes in lymphocyte subsets after ECP. CD4(+) and CD8(+) T-cell central and effector memory populations were enumerated by flow cytometry in a cohort of 37 patients postallogeneic transplantation with symptomatic cGVHD. Of the patients with symptomatic cGVHD, 7 were treated with ECP over 6 months and prospectively assessed for changes in lymphocyte subsets. There was a highly significant correlation of an increase in CD8(+) central memory cells and a concomitant decrease in CD4(+) central memory cells in patients with symptomatic cGVHD. These changes were not detected in patients without cGVHD posttransplantation. In all, 7 patients with cGVHD followed up prospectively during ECP treatment showed a statistically significant normalization of the pattern of CD4(+) and a trend toward normalization of CD8(+) central memory T cells coincident with improvement of cGVHD. These data indicate a high correlation between disturbances in the balance of central and effector memory populations and cGVHD suggesting use in following up responses to therapy. The normalization of central and effector memory populations in response to ECP coincident with clinical improvement of cGVHD support a correlation between these laboratory parameters and cGVHD. Further studies are needed to demonstrate whether laboratory measurements of the magnitude of changes in central and effector memory populations are useful prognostically or can be used to guide response to therapy. The contrasting change in central memory cells (CD8(+) increased versus CD4(+) decreased) in cGVHD provide support for recent reports suggesting unique differences in the differentiation pathways for CD8(+) versus CD4(+) T cells.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hmalech@nih.gov
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamashita
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.forename: Akua
authors.initials: A
authors.lastname: Kwatemaa
authors.forename: Effie
authors.initials: E
authors.lastname: Nomicos
authors.forename: Kathleen
authors.initials: K
authors.lastname: Castro
authors.forename: Robert
authors.initials: R
authors.lastname: Sokolic
authors.forename: Susan F
authors.initials: SF
authors.lastname: Foster
authors.forename: Mary
authors.initials: M
authors.lastname: Garofalo
authors.forename: Uimook
authors.initials: U
authors.lastname: Choi
authors.forename: Mark
authors.initials: M
authors.lastname: Ryherd
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Brown
authors.forename: Susan F
authors.initials: SF
authors.lastname: Leitman
authors.forename: Alan S
authors.initials: AS
authors.lastname: Wayne
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bishop
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
mesh_terms: D000328:Adult; D016516:CD4-CD8 Ratio / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011701:PUVA Therapy / Q000379:methods; D014184:Transplantation, Homologous