Cellular immune response

Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator

  1. Chris Ramsey1,†,
  2. Signe Hässler2,3,†,
  3. Per Marits2,3,
  4. Olle Kämpe2,
  5. Charles D. Surh1,
  6. Leena Peltonen4,
  7. Ola Winqvist2,3,*

Article first published online: 19 JAN 2006

DOI: 10.1002/eji.200535240

Issue

European Journal of Immunology

European Journal of Immunology

Volume 36, Issue 2, pages 305–317, February 2006

Additional Information

How to Cite

Ramsey, C., Hässler, S., Marits, P., Kämpe, O., Surh, Charles D., Peltonen, L. and Winqvist, O. (2006), Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator. Eur. J. Immunol., 36: 305–317. doi: 10.1002/eji.200535240

Author Information

  1. 1

    Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA

  2. 2

    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

  3. 3

    Karolinska Institutet, Department of Medicine, Unit of Clinical Allergy Research, Stockholm, Sweden

  4. 4

    Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland and Department of Medical Genetics, University of Helsinki, Helsinki, Finland

  1. †

    The first two authors contributed equally to this work.

*Karolinska Institutet, Department of Medicine, Unit of Clinical Allergy Research, Karolinska Hospital, 171 76 Stockholm, Sweden, Fax: +46-8-335724

Publication History

  1. Issue published online: 2 FEB 2006
  2. Article first published online: 19 JAN 2006
  3. Manuscript Accepted: 7 DEC 2005
  4. Manuscript Revised: 29 OCT 2005
  5. Manuscript Received: 7 JUL 2005

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Keywords:

  • Antigen-presenting cell;
  • Autoimmunity;
  • Clinical immunology;
  • Knockout mice;
  • Microarray

Abstract

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.

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