The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
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Published 7 November 2005. doi:10.1084/jem.20051135
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 9, 1213-1223
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ARTICLE

 TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand

Tomoki Ito1, Yui-Hsi Wang1, Omar Duramad1,2, Toshiyuki Hori3, Guy J. Delespesse4, Norihiko Watanabe1, F. Xiao-Feng Qin1, Zhengbin Yao5, Wei Cao1, and Yong-Jun Liu1,2

1 Center for Cancer Immunology Research, Department of Immunology, The University of Texas M.D. Anderson Cancer Center
2 The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030
3 Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
4 Allergy Research Laboratory, Research Center of Centre Hospitalier Université de Montreal, Notre Dame Hospital, Montreal, Quebec H2L 4M1, Canada
5 Tanox, Inc., Houston, TX 77025

CORRESPONDENCE Yong-Jun Liu: yjliu{at}mdanderson.org

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-{alpha} (TNF-{alpha}), 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-{alpha}, 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-{alpha}, 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-{alpha}–producing inflammatory Th cell responses.

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.


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