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Science 309 (5739): 1380-1384

Copyright © 2005 by the American Association for the Advancement of Science

Toll-Like Receptor 8-Mediated Reversal of CD4+ Regulatory T Cell Function

Guangyong Peng, Zhong Guo, Yukiko Kiniwa, Kui shin Voo, Weiyi Peng, Tihui Fu, Daniel Y. Wang, Yanchun Li, Helen Y. Wang, Rong-Fu Wang*

Abstract: CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity. These results suggest that TLR8 signaling could play a critical role in controlling immune responses to cancer and other diseases.

The Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.

* To whom correspondence should be addressed. E-mail: Rongfuw{at}

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Cutting Edge: TLR2 Directly Triggers Th1 Effector Functions.
T. Imanishi, H. Hara, S. Suzuki, N. Suzuki, S. Akira, and T. Saito (2007)
J. Immunol. 178, 6715-6719
   Abstract »    Full Text »    PDF »
Control of Regulatory T Cells and Cancer Immunity by Toll-Like Receptors.
R.-F. Wang (2007)
Am. Assoc. Cancer Res. Educ. Book 2007, 177-182
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Immunopathogenesis of IBD: insufficient suppressor function in the gut?.
I L Huibregtse, A U van Lent, and S J H van Deventer (2007)
Gut 56, 584-592
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Human CD4+CD25low Adaptive T Regulatory Cells Suppress Delayed-Type Hypersensitivity during Transplant Tolerance.
Q. Xu, J. Lee, E. Jankowska-Gan, J. Schultz, D. A. Roennburg, L. D. Haynes, S. Kusaka, H. W. Sollinger, S. J. Knechtle, A. M. VanBuskirk, et al. (2007)
J. Immunol. 178, 3983-3995
   Abstract »    Full Text »    PDF »
TLR4 Hyperresponsiveness via Cell Surface Expression of Heat Shock Protein gp96 Potentiates Suppressive Function of Regulatory T Cells.
J. Dai, B. Liu, S. M. Ngoi, S. Sun, A. T. Vella, and Z. Li (2007)
J. Immunol. 178, 3219-3225
   Abstract »    Full Text »    PDF »
TLR9 ligand enhances proliferation of rat CD4+ T cell and modulates suppressive activity mediated by CD4+ CD25+ T cell.
E. Chiffoleau, J.-M. Heslan, M. Heslan, C. Louvet, T. Condamine, and M.-C. Cuturi (2007)
Int. Immunol. 19, 193-201
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NK and CD4 Cells Collaborate to Protect against Melanoma Tumor Formation in the Brain.
R. M. Prins, D. D. Vo, H. Khan-Farooqi, M.-Y. Yang, H. Soto, J. S. Economou, L. M. Liau, and A. Ribas (2006)
J. Immunol. 177, 8448-8455
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Human Effector CD8+ T Lymphocytes Express TLR3 as a Functional Coreceptor.
J. Tabiasco, E. Devevre, N. Rufer, B. Salaun, J.-C. Cerottini, D. Speiser, and P. Romero (2006)
J. Immunol. 177, 8708-8713
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Immunostimulatory combinations: designing the next generation of vaccine adjuvants.
R. S. Kornbluth and G. W. Stone (2006)
J. Leukoc. Biol. 80, 1084-1102
   Abstract »    Full Text »    PDF »
TLR agonists promote ERK-mediated preferential IL-10 production of regulatory dendritic cells (diffDCs), leading to NK-cell activation.
C. Qian, X. Jiang, H. An, Y. Yu, Z. Guo, S. Liu, H. Xu, and X. Cao (2006)
Blood 108, 2307-2315
   Abstract »    Full Text »    PDF »

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