IMMUNOBIOLOGY Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous allospecific T-cell responses in vivo

Abstract

Dendritic cells (DCs) genetically engi-neered to overexpress CD95 (Fas) ligand (CD95L-DC) were proposed as tools to induce peripheral tolerance to alloanti-gens. 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, al-though 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 allo-grafts that were otherwise tolerated in the context of this single weak major histo-compatibility complex (MHC) class I in-compatibility. Massive neutrophil infil-trates depending on interleukin (IL)–1 signaling were observed at sites of CD95L-DC injection. Experiments in IL-1 receptor–deficient mice or in animals in-jected with depleting anti-Gr1 monoclo-nal antibody (mAb) established that neu-trophil recruitment is required for the development of vigorous T-cell responses after injection of CD95L-DC in vivo

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