During an immune response, activated antigen (Ag)-specific T cells condition dendritic cells (DCs) to enhance DC function and survival within the inflamed draining lymph node (LN). It has been difficult to ascertain the role of the tumor necrosis factor (TNF) superfamily member lymphotoxin-αβ (LTαβ) in this process because signaling through the LTβ-receptor (LTβR) controls multiple aspects of lymphoid tissue organization. To resolve this, we have used an in vivo system where the expression of TNF family ligands is manipulated only on the Ag-specific T cells that interact with and condition Ag-bearing DCs. We report that LTαβ is a critical participant required for optimal DC function, independent of its described role in maintaining lymphoid tissue organization. In the absence of LTαβ or CD40L on Ag-specific T cells, DC dysfunction could be rescued in vivo via CD40 or LTβR stimulation, respectively, suggesting that these two pathways cooperate for optimal DC conditioning.
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14 May 2007
Article|
April 23 2007
Expression of lymphotoxin-αβ on antigen-specific T cells is required for DC function
Leslie E. Summers-deLuca,
Leslie E. Summers-deLuca
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
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Douglas D. McCarthy,
Douglas D. McCarthy
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
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Bojana Cosovic,
Bojana Cosovic
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
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Lesley A. Ward,
Lesley A. Ward
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
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Calvin C. Lo,
Calvin C. Lo
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
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Stefanie Scheu,
Stefanie Scheu
2Institute of Medical Microbiology, Universität Düsseldorf, D-40225 Düsseldorf, Germany
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Klaus Pfeffer,
Klaus Pfeffer
2Institute of Medical Microbiology, Universität Düsseldorf, D-40225 Düsseldorf, Germany
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Jennifer L. Gommerman
Jennifer L. Gommerman
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
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Leslie E. Summers-deLuca
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
Douglas D. McCarthy
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
Bojana Cosovic
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
Lesley A. Ward
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
Calvin C. Lo
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
Stefanie Scheu
2Institute of Medical Microbiology, Universität Düsseldorf, D-40225 Düsseldorf, Germany
Klaus Pfeffer
2Institute of Medical Microbiology, Universität Düsseldorf, D-40225 Düsseldorf, Germany
Jennifer L. Gommerman
1Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
CORRESPONDENCE Jennifer Gommerman: [email protected]
Abbreviations used: FDC, follicular dendritic cell; HEV, high endothelial venule; HVEM, herpes virus entry mediator; LT, lymphotoxin; LTαβ, LT-αβ; LTβR, LTβ-receptor; SI, stimulation index; TRAF, TNF receptor–associated factor.
Received:
September 13 2006
Accepted:
March 21 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (5): 1071–1081.
Article history
Received:
September 13 2006
Accepted:
March 21 2007
Citation
Leslie E. Summers-deLuca, Douglas D. McCarthy, Bojana Cosovic, Lesley A. Ward, Calvin C. Lo, Stefanie Scheu, Klaus Pfeffer, Jennifer L. Gommerman; Expression of lymphotoxin-αβ on antigen-specific T cells is required for DC function . J Exp Med 14 May 2007; 204 (5): 1071–1081. doi: https://doi.org/10.1084/jem.20061968
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