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Type: Journal article
Title: Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input
Author: White, A.
Withers, D.
Parnell, S.
Scott, H.
Finke, D.
Lane, P.
Jenkinson, E.
Anderson, G.
Citation: European Journal of Immunology, 2008; 38(4):942-947
Publisher: Wiley-V C H Verlag GMBH
Issue Date: 2008
ISSN: 0014-2980
Statement of
Andrea J. White, David R. Withers, Sonia M. Parnell, Hamish S. Scott, Daniela Finke, Peter J. L. Lane, Eric J. Jenkinson and Graham Anderson
Abstract: Intrathymic deletion of immature thymocytes that express self-reactive TCR specificities is essential in the generation of self tolerance. Medullary thymic epithelial cells (mTEC) expressing the transcriptional regulator Aire play a key role in this process by regulating expression of tissue-restricted antigens to ensure tolerance to peripheral tissues. Here, we have analysed the cellular and molecular requirements for the initial appearance of Aire+ mTEC in the embryonic thymus, in addition to their persistence in the adult thymus. Analysis of thymic ontogeny shows that the emergence of embryonic Aire+ mTEC occurs prior to the appearance of mature thymocytes, and depends upon lymphoid tissue inducer cells expressing retinoic acid receptor-related orphan receptor gamma. In the adult thymus, we show that Aire+ mTEC develop in the absence of thymocyte positive and negative selection and CD40 signalling, but are present at reduced frequency. Collectively these data support a model where the initial differentiation of Aire+ mTEC involves receptor activator of NF-kappaB (RANK)-RANKL interactions with lymphoid tissue inducer cells, with subsequent mTEC turnover and/or survival involving CD40-mediated signalling following interactions with mature CD4+ thymocytes that express CD40L.
Keywords: Cell differentiation
Lymphoid organs
DOI: 10.1002/eji.200738052
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