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Prepublished online as a Blood First Edition Paper on October 17, 2002; DOI 10.1182/blood-2002-07-2042.
Submitted July 10, 2002
Accepted September 30, 2002
Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous allospecific T cell responses in vivo
Sofia Buonocore, Frederic Paulart, Alain Le Moine, Michel Y Braun, Isabelle Salmon, Sonja Van Meirvenne, Kris Thielemans, Michel Goldman, and Veronique Flamand*
Experimental Immunology, Universite Libre de Bruxelles, Brussels, Belgium
Department of Pathology, Universite Libre de Bruxelles, Brussels, Belgium
Laboratory of Physiology, Medical School of Vrije Universiteit Brussel, Brussels, Belgium
* Corresponding author; email: vflamand{at}ulb.ac.be.
Dendritic cells (DC) genetically engineered to overexpress CD95 (Fas) ligand (CD95L-DC) were proposed as tools to induce peripheral tolerance to alloantigens. Herein, we observed that CD95L-DC obtained after retroviral gene transfer in bone marrow (BM) precursors derived from CD95-deficient (lpr/lpr) mice elicit much stronger allospecific type 1 helper T cell and cytotoxic T cell activities than control DC upon injection in vivo although they induce lower T cell responses in vitro. Indeed, a single injection of CD95L-DC prepared from C57BL/6 mice was sufficient to prime bm13 recipients for acute rejection of C57BL/6 skin allografts which were otherwise tolerated in the context of this single weak MHC class I incompatibility. Massive neutrophil infiltrates depending on IL1 signaling were observed at sites of CD95L-DC injection. Experiments in IL1-receptor-deficient mice or in animals injected with depleting anti-Gr1 mAb established that neutrophils recruitment is required for the development of vigorous T cell responses after injection of CD95L-DC in vivo.
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