The Journal of Experimental Medicine
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Published 21 April 2003. doi:10.1084/jem.20030240
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© Rockefeller University Press, 0022-1007/2003/4/1059 $5.00
The Journal of Experimental Medicine, Volume 197, Number 8, 1059-1063

Brief Definitive Report

Human Dendritic Cells Activated by TSLP and CD40L Induce Proallergic Cytotoxic T Cells

Michel Gilliet, Vassili Soumelis, Norihiko Watanabe, Shino Hanabuchi, Svetlana Antonenko, Rene de Waal-Malefyt and Yong-Jun Liu

DNAX Research Institute, Palo Alto, CA 94304

Address correspondence to Yong-Jun Liu, Department of Immunology, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone: 713-792-8575; Fax: 713-794-1322; E-mail: yjliu{at}mdanderson.org; or Vassili Soumelis, Department of Hematology and Bone Marrow Transplantation, Necker Hospital, 149 rue de Sèvres, 75015 Paris, France. Phone: 33-(0)1-44-49-5286; E-mail: soumelis{at}necker.fr

Human thymic stromal lymphopoietin (TSLP) is a novel epithelial cell–derived cytokine, which induces dendritic cell (DC)-mediated CD4+ T cell responses with a proallergic phenotype. Although the participation of CD8+ T cells in allergic inflammation is well documented, their functional properties as well as the pathways leading to their generation remain poorly understood. Here, we show that TSLP-activated CD11c+ DCs potently activate and expand naive CD8+ T cells, and induce their differentiation into interleukin (IL)-5 and IL-13–producing effectors exhibiting poor cytolytic activity. Additional CD40L triggering of TSLP-activated DCs induced CD8+ T cells with potent cytolytic activity, producing large amounts of interferon (IFN)-{gamma}, while retaining their capacity to produce IL-5 and IL-13. These data further support the role of TSLP as initial trigger of allergic T cell responses and suggest that CD40L-expressing cells may act in combination with TSLP to amplify and sustain pro-allergic responses and cause tissue damage by promoting the generation of IFN-{gamma}–producing cytotoxic effectors.

Key Words: TSLP • CD11c+ DC • CD8+ T lymphocyte • allergy • cytotoxicity


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