Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator
2006 (English)In: European Journal of Immunology, Vol. 36, no 2, 305-317 p.Article in journal (Refereed) Published
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.
Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-75251DOI: doi:10.1002OAI: oai:DiVA.org:uu-75251DiVA: diva2:103161