Elimination of Antigen-Presenting Cells and Autoreactive T Cells by Fas Contributes to Prevention of Autoimmunity

Fas (also known as Apo-1 and CD95) receptor has been suggested to control T cell expansion by triggering T cell-autonomous apoptosis. This paradigm is based on the extensive lymphoproliferation and systemic autoimmunity in mice and humans lacking Fas or its ligand. However, with systemic loss of Fas...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2007-05, Vol.26 (5), p.629-641
Main Authors: Stranges, Peter B., Watson, Jessica, Cooper, Cristie J., Choisy-Rossi, Caroline-Morgane, Stonebraker, Austin C., Beighton, Ryan A., Hartig, Heather, Sundberg, John P., Servick, Stein, Kaufmann, Gunnar, Fink, Pamela J., Chervonsky, Alexander V.
Format: Article
Language:English
Subjects:
Animals
Antigen-Presenting Cells - immunology
Antigen-Presenting Cells - metabolism
Antigens - immunology
Autoimmunity - immunology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
CD11c Antigen - genetics
CD11c Antigen - metabolism
CELLCYCLE
CELLIMMUNO
Cells, Cultured
Cytotoxicity
Dendritic Cells - immunology
Dendritic Cells - metabolism
fas Receptor - genetics
fas Receptor - immunology
Gene Deletion
Gene Expression Regulation
Immunoglobulin Heavy Chains - immunology
Ligands
Lymphocyte Activation - immunology
Lymphocytes
Mice
Mice, Transgenic
MOLIMMUNO
Peptides
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Viral infections
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Summary:Fas (also known as Apo-1 and CD95) receptor has been suggested to control T cell expansion by triggering T cell-autonomous apoptosis. This paradigm is based on the extensive lymphoproliferation and systemic autoimmunity in mice and humans lacking Fas or its ligand. However, with systemic loss of Fas, it is unclear whether T cell-extrinsic mechanisms contribute to autoimmunity. We found that tissue-specific deletion of Fas in mouse antigen-presenting cells (APCs) was sufficient to cause systemic autoimmunity, implying that normally APCs are destroyed during immune responses via a Fas-mediated mechanism. Fas expression by APCs was increased by exposure to microbial stimuli. Analysis of mice with Fas loss restricted to T cells revealed that Fas indeed controls autoimmune T cells, but not T cells responding to strong antigenic stimulation. Thus, Fas-dependent elimination of APCs is a major regulatory mechanism curbing autoimmune responses and acts in concert with Fas-mediated regulation of chronically activated autoimmune T cells.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2007.03.016