Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Brüggen, MC; Klein, I; Greinix, H; Bauer, W; Kuzmina, Z; Rabitsch, W; Kalhs, P; Petzelbauer, P; Knobler, R; Stingl, G; Stary, G.
Diverse T-cell responses characterize the different manifestations of cutaneous graft-versus-host disease.
Blood. 2014; 123(2): 290-299.
Doi: 10.1182/blood-2013-07-514372
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- Co-Autor*innen der Med Uni Graz
- Greinix Hildegard
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Biopsy -
- Cytokines - metabolism
- Female -
- Graft vs Host Disease - etiology Graft vs Host Disease - pathology
- Hematopoietic Stem Cell Transplantation - adverse effects
- Humans -
- Male -
- Middle Aged -
- Receptors, Cytokine - metabolism
- Retrospective Studies -
- Skin Diseases - etiology Skin Diseases - pathology
- T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism
- Th1 Cells - immunology Th1 Cells - metabolism
- Th2 Cells - immunology Th2 Cells - metabolism