title: Diverse T-cell responses characterize the different manifestations of cutaneous graft-versus-host disease.
abstract: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HCT) and can present in an acute (aGVHD), a chronic lichenoid (clGVHD), and a chronic sclerotic form (csGVHD). It is unclear whether similar or different pathomechanisms lead to these distinct clinical presentations. To address this issue, we collected lesional skin biopsies from aGVHD (n = 25), clGVHD (n = 17), and csGVHD (n = 7) patients as well as serial nonlesional biopsies from HCT recipients (prior to or post-HCT) (n = 14) and subjected them to phenotypic and functional analyses. Our results revealed striking differences between aGVHD and clGVHD. In aGVHD, we found a clear predominance of T helper (Th)2 cytokines/chemokines and, surprisingly, of interleukin (IL)-22 messenger RNA as well as an increase of IL-22-producing CD4(+) T cells. Thymic stromal lymphopoietin, a cytokine skewing the immune response toward a Th2 direction, was elevated at day 20 to 30 post-HCT in the skin of patients who later developed aGVHD. In sharp contrast to aGVHD, the immune response occurring in clGVHD showed a mixed Th1/Th17 signature with upregulated Th1/Th17 cytokine/chemokine transcripts and elevated numbers of interferon-γ- and IL-17-producing CD8(+) T cells. Our findings shed new light on the T-cell responses involved in the different manifestations of cutaneous GVHD and identify molecular signatures indicating the development of the disease.
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases.
authors.forename: Marie-Charlotte
authors.initials: MC
authors.lastname: Brüggen
authors.forename: Irene
authors.initials: I
authors.lastname: Klein
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bauer
authors.forename: Zoya
authors.initials: Z
authors.lastname: Kuzmina
authors.forename: Werner
authors.initials: W
authors.lastname: Rabitsch
authors.forename: Peter
authors.initials: P
authors.lastname: Kalhs
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
authors.forename: Robert
authors.initials: R
authors.lastname: Knobler
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.forename: Georg
authors.initials: G
authors.lastname: Stary
mesh_terms: D000328:Adult; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018121:Receptors, Cytokine / Q000378:metabolism; D012189:Retrospective Studies; D012871:Skin Diseases / Q000209:etiology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin