We recently showed that dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) prime naive CD4+ T cells to differentiate into T helper type 2 (Th2) cells that produced high amounts of tumor necrosis factor-α (TNF-α), but no interleukin (IL)-10. Here we report that TSLP induced human DCs to express OX40 ligand (OX40L) but not IL-12. TSLP-induced OX40L on DCs was required for triggering naive CD4+ T cells to produce IL-4, -5, and -13. We further revealed the following three novel functional properties of OX40L: (a) OX40L selectively promoted TNF-α, but inhibited IL-10 production in developing Th2 cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and (c) OX40L exacerbated IL-12–induced Th1 cell inflammation by promoting TNF-α, while inhibiting IL-10. We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10–producing regulatory Th cell responses into TNF-α–producing inflammatory Th cell responses.
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7 November 2005
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November 07 2005
TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand
Tomoki Ito,
Tomoki Ito
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
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Yui-Hsi Wang,
Yui-Hsi Wang
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
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Omar Duramad,
Omar Duramad
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
2The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030
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Toshiyuki Hori,
Toshiyuki Hori
3Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
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Guy J. Delespesse,
Guy J. Delespesse
4Allergy Research Laboratory, Research Center of Centre Hospitalier Université de Montreal, Notre Dame Hospital, Montreal, Quebec H2L 4M1, Canada
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Norihiko Watanabe,
Norihiko Watanabe
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
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F. Xiao-Feng Qin,
F. Xiao-Feng Qin
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
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Zhengbin Yao,
Zhengbin Yao
5Tanox, Inc., Houston, TX 77025
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Wei Cao,
Wei Cao
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
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Yong-Jun Liu
Yong-Jun Liu
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
2The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030
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Tomoki Ito
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
Yui-Hsi Wang
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
Omar Duramad
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
2The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030
Toshiyuki Hori
3Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
Guy J. Delespesse
4Allergy Research Laboratory, Research Center of Centre Hospitalier Université de Montreal, Notre Dame Hospital, Montreal, Quebec H2L 4M1, Canada
Norihiko Watanabe
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
F. Xiao-Feng Qin
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
Zhengbin Yao
5Tanox, Inc., Houston, TX 77025
Wei Cao
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
Yong-Jun Liu
1Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
2The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030
CORRESPONDENCE Yong-Jun Liu: [email protected]
Abbreviations used in this paper: APC, allophycocyanin; CD40L, CD40 ligand; mDC, myeloid DC; OX40L, OX40 ligand; TLR, Toll-like receptor; TSLP, thymic stromal lymphopoietin.
T. Ito and Y.-H. Wang contributed equally to this work.
Received:
July 06 2005
Accepted:
September 06 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (9): 1213–1223.
Article history
Received:
July 06 2005
Accepted:
September 06 2005
Citation
Tomoki Ito, Yui-Hsi Wang, Omar Duramad, Toshiyuki Hori, Guy J. Delespesse, Norihiko Watanabe, F. Xiao-Feng Qin, Zhengbin Yao, Wei Cao, Yong-Jun Liu; TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand . J Exp Med 7 November 2005; 202 (9): 1213–1223. doi: https://doi.org/10.1084/jem.20051135
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