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Pediatric Rheumatology

, 6:P124 | Cite as

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

  • MM Hauri-Hohl
  • GA Hollander
Open Access
Poster presentation

Keywords

Hematopoietic Stem Cell Transplantation Cell Clone Negative Selection Vitro Assay Downstream Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Hematopoietic stem cell transplantation (HSCT) is considered 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-constructing a functional immune system tolerant to auto-antigens. The re-emergence of T cell immunity following myeloablation largely depends on thymic de novo production of naïve T cells. The thymic stroma – mainly consisting of thymic epithelium (TE) – is responsible for the attraction of thymocyte precursor cells, support of developing T cells and appropriate positive and negative selection 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 detrimental 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.

Copyright information

© Hauri-Hohl and Hollander; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • MM Hauri-Hohl
    • 1
  • GA Hollander
    • 1
  1. 1.Pediatric ImmunologyCenter for BiomedicineBaselSwitzerland

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