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Prepublished online as a Blood First Edition Paper on October 17, 2002; DOI 10.1182/blood-2002-07-2042.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1469-1476
IMMUNOBIOLOGY
Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous
allospecific T-cell responses in vivo
Sofia Buonocore,
Frédéric Paulart,
Alain Le Moine,
Michel Braun,
Isabelle Salmon,
Sonja Van Meirvenne,
Kris Thielemans,
Michel Goldman, and
Véronique Flamand
From the Laboratory of Experimental Immunology,
Université Libre de Bruxelles; Department of Pathology,
Hôpital Erasme, Université Libre de Bruxelles; and
Laboratory of Physiology, Medical School of Vrije Universiteit Brussel,
Brussels, Belgium.
Dendritic cells (DCs) 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 DCs
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 that were otherwise tolerated in the context of
this single weak major histocompatibility complex (MHC) class I
incompatibility. Massive neutrophil infiltrates depending on
interleukin (IL)-1 signaling were observed at sites of CD95L-DC
injection. Experiments in IL-1 receptor-deficient mice or in animals
injected with depleting anti-Gr1 monoclonal antibody (mAb) established
that neutrophil recruitment is required for the development of vigorous
T-cell responses after injection of CD95L-DC in vivo.
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