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Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. CKMF. (immunterapi (Ola Winqvist))
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. CKMF. (immunterapi (Ola Winqvist))
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. CKMF. (endokrin autoimmunitet)
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2006 (English)In: European Journal of Immunology, Vol. 36, no 2, 305-317 p.Article in journal (Refereed) Published
Abstract [en]

Patients with autoimmune polyendocrine syndrome type I (APS I)suffer from endocrine and non-endocrine disorders due to mutations in the autoimmune regulator gene (AIRE). Mouse Aire is expressed both in thymic medullary epithelial cells and in peripheral antigen-presenting cells, suggesting a role in both central and peripheral tolerance. We here report that Aire(-/-) dendritic cells (DC) activate naive T cells more efficiently than do Aire(+/+) DC. Expression array analyses of Aire(-/-) DC revealed differential regulation of 68 transcripts, among which, the vascular cell adhesion molecule-1 (VCAM-1) transcript was up-regulated in Aire(-/-) DC. Concurrently, the expression of the VCAM-1 protein was up-regulated on both Aire(-/-) DC and monocytes from APS I patients. Blocking the interaction of VCAM-1 prevented enhanced Aire(-/-) DC stimulation of T cell hybridomas. We determined an increased number of DC in spleen and lymph nodes and of monocytes in the blood from Aire(-/-) mice, and an increased number of blood monocytes in APS I patients. Our findings imply a role for Aire in peripheral DC regulation of T cell activation, and suggest that Aire participates in peripheral tolerance.

Place, publisher, year, edition, pages
2006. Vol. 36, no 2, 305-317 p.
National Category
Immunology in the medical area
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URN: urn:nbn:se:uu:diva-75251DOI: doi:10.1002OAI: oai:DiVA.org:uu-75251DiVA: diva2:103161
Available from: 2006-02-02 Created: 2006-02-02 Last updated: 2011-01-11

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Hässler, SigneMarits, PerKämpe, OllePeltonen, LeenaWinqvist, Ola

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