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Vol. 16, No. 1, 2009
Issue release date: January 2009
Section title: Original Paper
Neuroimmunomodulation 2009;16:35–44
(DOI:10.1159/000179665)

Aire and Foxp3 Expression in a Particular Microenvironment for T Cell Differentiation

Hansenne I. · Louis C. · Martens H. · Dorban G. · Charlet-Renard C. · Peterson P. · Geenen V.
aCenter of Immunology, Institute of Pathology, and bLaboratory of Histology, University of Liege, Liege-Sart Tilman, Belgium; cMolecular Pathology, University of Tartu, Tartu, Estonia

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 4/15/2008
Accepted: 7/11/2008
Published online: 12/15/2008

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 1

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM

Abstract

Objective: The thymus is the primary lymphoid organ responsible for T cell development and the establishment of central self-tolerance. Among thymic epithelial cells, thymic nurse cells (TNC) interact closely with immature thymocytes and constitute a special microenvironment for T cell differentiation and selection. In addition, TNC express neuroendocrine self-antigens such as oxytocin and insulin-like growth factor-2, whose intrathymic transcription is regulated by the autoimmune regulator gene/protein (Aire). Both effector and natural regulatory T cell (nTreg) lineages develop in the thymus, but the mechanisms leading to nTreg selection in the thymus are still unclear. Foxp3 is the most specific nTreg marker that is required for nTreg functional activity, but not for engagement into the Treg lineage. Aire has been suggested to be a potential factor implicated in this role. The objective of this study was to characterize Aire and Foxp3 expression in TNC/thymocyte complexes. Methods:Aire and Foxp3 expression was investigated by RT-qPCR in TNC/thymocyte complexes isolated by enzymatic digestion and sedimentation. Aire and Foxp3 proteins were located by confocal microscopy and specific immunocytochemistry. Results: Both Aire and Foxp3 transcripts were detected in TNC/thymocyte complexes. Foxp3 was detected in the nucleus of thymocytes internalized into TNC. Aire was located mainly in TNC cytoplasm and, although to a lower degree, in the nucleus of some TNC-associated thymocytes. Conclusions: Aire and Foxp3 are present in the particular TNC microenvironment which has previously been shown to support thymic selection. The differential localization of these two markers suggests a role for TNC in nTreg development.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 4/15/2008
Accepted: 7/11/2008
Published online: 12/15/2008

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 1

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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