CD40-CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4+ T cells.

Details

Serval ID
serval:BIB_56C1EDD66217
Type
Article: article from journal or magazin.
Collection
Publications
Title
CD40-CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4+ T cells.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Iezzi G., Sonderegger I., Ampenberger F., Schmitz N., Marsland B.J., Kopf M.
ISSN
1091-6490[electronic]
Publication state
Published
Issued date
2009
Volume
106
Number
3
Pages
876-881
Language
english
Abstract
IL-17-producing CD4(+) T cells have been recognized as key players in organ-related autoimmune disease; however, the parameters that govern their development are yet to be elucidated fully. By using both in vivo and in vitro systems, we have investigated the role of antigen dose, pathogen-associated molecular patterns, and CD40-CD40 ligand (CD40L) cross-talk in Th17 differentiation. We found that the strength of antigenic stimulation critically influenced the extent of Th17 differentiation, because high, but not low or intermediate, antigen concentrations led to IL-17 production. Strong antigenic stimulation of T cells up-regulated CD40L expression, which in concert with certain microbial stimuli (i.e., cytosine phosphate guanine, curdlan, and zymosan) synergistically increased dendritic cell (DC) IL-6 production and Th17 polarization. CD40-deficient DCs exhibited reduced cytokine release and failed to drive Th17 development in vitro. These results were confirmed in vivo where the absence of CD40-CD40L cross-talk was found to prevent the expansion of IL-17-producing cells and accordingly the development of experimental autoimmune encephalitis. Our data demonstrate that CD40-CD40L cross-talk is important for Th17 development by translating strong T cell receptor and microbial stimuli into IL-6 production.
Keywords
Animals, Antigens/immunology, Antigens, CD40/physiology, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/physiology, CD40 Ligand/physiology, Cell Differentiation, Cell Polarity, Dendritic Cells/physiology, Encephalomyelitis, Autoimmune, Experimental/immunology, Interleukin-12 Subunit p35/biosynthesis, Interleukin-17/biosynthesis, Interleukin-6/biosynthesis, Listeria monocytogenes/immunology, Mice, Mice, Inbred C57BL, Th1 Cells/immunology, Transforming Growth Factor beta/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
18/01/2010 14:02
Last modification date
20/08/2019 15:10
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