Unique patterns of CD8+ T-cell-mediated organ damage in the Act-mOVA/OT-I model of acute graft-versus-host disease. (NDA@SZTAKI, Nemzeti Digitális Adattár, National Digital Data Archive)

Unique patterns of CD8+ T-cell-mediated organ damage in the Act-mOVA/OT-I model of acute graft-versus-host disease.

Metaadatok

Tartalom:	http://real.mtak.hu/35398/
Archívum:	MTA Könyvtár
Gyûjtemény:	Status = In Press Type = Article
Cím:	Unique patterns of CD8+ T-cell-mediated organ damage in the Act-mOVA/OT-I model of acute graft-versus-host disease.
Létrehozó:	Ã‰rsek, Barbara Lupsa, Nikolett PÃ³cza, PÃ©ter TÃ³th, Anett HorvÃ¡th, Andor MolnÃ¡r, Viktor Bagita, Bence Bencsik, AndrÃ¡s Hegyesi, Hargita Matolcsy, AndrÃ¡s BuzÃ¡s, Edit I. PÃ³s, ZoltÃ¡n
Kiadó:	Springer
Dátum:	2016-04-30
Téma:	R1 Medicine (General) / orvostudomÃ¡ny Ã¡ltalÃ¡ban
Tartalmi leírás:	T-cell receptor (TCR)-transgenic models of acute graft-versus-host disease (aGvHD) offer a straightforward and highly controlled approach to study the mechanisms and consequences of T-cell activation following allogeneic hematopoietic stem cell transplantation (aHSCT). Here, we report that aHSCT involving OT-I mice as donors, carrying an ovalbumin-specific CD8+ TCR, and Act-mOVA mice as recipients, expressing membrane-bound ovalbumin driven by the Î²-actin promoter, induces lethal aGvHD in a CD8+ T-cell-dependent, highly reproducible manner, within 4-7Â days. Tracking of UBC-GFP/OT-I graft CD8+ T cells disclosed heavy infiltration of the gastrointestinal tract, liver, and lungs at the onset of the disease, and histology confirmed hallmark features of gastrointestinal aGVHD, hepatic aGvHD, and aGvHD-associated lymphocytic bronchitis in infiltrated organs. However, T-cell infiltration was virtually absent in the skin, a key target organ of human aGvHD, and histology confirmed the absence of cutaneous aGVHD, as well. We show that the model allows studying CD8+ T-cell responses in situ, as selective recovery of graft CD45.1/OT-I CD8+ T cells from target organs is simple and feasible by automated tissue dissociation and subsequent cell sorting. Assessment of interferon-gamma production by flow cytometry, granzyme-B release by ELISA, TREC assay, and whole-genome gene expression profiling confirmed that isolated graft CD8+ T cells remained intact, underwent clonal expansion, and exerted effector functions in all affected tissues. Taken together, these data demonstrate that the OT-I/Act-mOVA model is suitable to study the CD8+ T-cell-mediated effector mechanisms in a disease closely resembling fatal human gastrointestinal and hepatic aGVHD that may develop after aHSCT using HLA-matched unrelated donors.
Nyelv:	angol
Típus:	Article PeerReviewed info:eu-repo/semantics/article
Formátum:	text
Azonosító:	http://real.mtak.hu/35398/1/Ersek%20et%20al%20v.1.04%20revi... Ã‰rsek, Barbara and Lupsa, Nikolett and PÃ³cza, PÃ©ter and TÃ³th, Anett and HorvÃ¡th, Andor and MolnÃ¡r, Viktor and Bagita, Bence and Bencsik, AndrÃ¡s and Hegyesi, Hargita and Matolcsy, AndrÃ¡s and BuzÃ¡s, Edit I. and PÃ³s, ZoltÃ¡n (2016) Unique patterns of CD8+ T-cell-mediated organ damage in the Act-mOVA/OT-I model of acute graft-versus-host disease. Cellular and Molecular Life Sciences. pp. 1-33. ISSN 1420-9071 (In Press)
Kapcsolat:	http://real.mtak.hu/35398/