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Cited by 203

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

Open access
Iezzi, Giandomenica, Sonderegger, Ivo, Ampenberger, Franziska, Schmitz, Nicole, Marsland, Benjamin J., Kopf, Manfred·2009·Proceedings of the National Academy of Sciences

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.

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Metadata

Authors
Iezzi, G., Sonderegger, I., Ampenberger, F., Schmitz, N., Marsland, B. J., & Kopf, M.
Venue
Proceedings of the National Academy of Sciences
Published
2009-01-20
Volume
106
Issue
3
Pages
876-881
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2012868103
Cited by
203
References
11
FWCI
7.64
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: CD40–CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4 + T cells. https://app.cochat.ai/papers/10.1073/pnas.0810769106
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Iezzi, G., Sonderegger, I., Ampenberger, F., Schmitz, N., Marsland, B. J., & Kopf, M. (2009). CD40–CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4 + T cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0810769106

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