Hauri-Hohl, MM

Hollander, GA

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MM Hauri-Hohl

GA Hollander

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TGF-beta signalling contributes to thymic epithelial cell damage and regeneration following myeloablative conditioning and stem-cell transplantation

Hauri-Hohl MM

Hollander GA

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Pediatric Rheumatology

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Pediatric Rheumatology
Open AccessPoster presentation
TGF-beta signalling contributes to thymic epithelial cell damage 
and regeneration following myeloablative conditioning and 
stem-cell transplantation
MM Hauri-Hohl* and GA Hollander
Address: Pediatric Immunology, Center for Biomedicine, Basel, Switzerland
* Corresponding author    
Hematopoietic stem cell transplantation (HSCT) is con-
sidered a potentially curative therapy for a number of
severe autoimmune diseases. The rationale consists of
deleting auto-reactive T and/or B cell clones and re-con-
structing a functional immune system tolerant to auto-
antigens. The re-emergence of T cell immunity following
myeloablation largely depends on thymic de novo pro-
duction of naïve T cells. The thymic stroma – mainly con-
sisting of thymic epithelium (TE) – is responsible for the
attraction of thymocyte precursor cells, support of devel-
oping T cells and appropriate positive and negative selec-
tion of a broad T cell receptor repertoire. Several reports
including ours have demonstrated a negative impact of
conditioning on TE numbers and function, which results
in delayed T cell reconstitution. We have recently
described the contribution of TGF-β signalling to thymic
epithelial cell damage after irradiation, yet the underlying
molecular mechanisms remain elusive.
In this report we analyse the involvement of TGF-β family
members and downstream molecules in TE injury and
regeneration following irradiation using different mouse
models and in vitro assays. We demonstrate the detrimen-
tal effects of active TGF-β protein released by thymocytes
early after irradiation on proliferation and phenotype of
TE with a direct consequence on the dynamics of T cell
reconstitution. The particular importance of TE in the
process of efficient T cell development necessitates the
development of strategies to protect the TE compartment
and enhance its restoration in the context of pre-HSCT
conditioning.
from 15th Paediatric Rheumatology European Society (PreS) Congress
London, UK. 14–17 September 2008
Published: 15 September 2008
Pediatric Rheumatology 2008, 6(Suppl 1):P124 doi:10.1186/1546-0096-6-S1-P124
<supplement> <title> <p>15<sup>th </sup>Paediatric Rheumatology European Society (PreS) Congress</p> </title> <editor>Wietse Kuis, Patricia Woo, Angelo Ravelli, Hermann Girschick, Michaël Hofer, Johannes Roth, Rotraud K Saurenmann, Alberto Martini, Pavla Dolezova, Janjaap van der Net, Pierre Quartier, Lucy Wedderburn and Jan Scott</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/PDF/1546-0096-6-S1-full.pdf">here</a>.</note> </supplement>
This abstract is available from: http://www.ped-rheum.com/content/6/S1/P124
© 2008 Hauri-Hohl and Hollander; licensee BioMed Central Ltd. 


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TGF-beta signalling contributes to thymic epithelial cell damage and regeneration following myeloablative conditioning and stem-cell transplantation

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