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Increased antigen p...
Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator
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- Hässler, Signe (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Autoimmuna sjukdomar (Kämpe),CKMF,immunterapi (Ola Winqvist)
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Ramsey, Chris (author)
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- Marits, Per (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Autoimmuna sjukdomar (Kämpe),CKMF,immunterapi (Ola Winqvist)
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- Kämpe, Olle (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Autoimmuna sjukdomar (Kämpe),CKMF,endokrin autoimmunitet
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Surh, Charles D. (author)
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Peltonen, Leena (author)
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- Winqvist, Ola (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinska vetenskaper,Autoimmuna sjukdomar (Kämpe),CKMF,immunterapi (Ola Winqvist)
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Surh, CA (author)
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(creator_code:org_t)
- Wiley, 2006
- 2006
- English.
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 36:2, s. 305-317
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- MEDICINE
- MEDICIN
- Immunobiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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