Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous allospecific T-cell responses in vivo.
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.
Buonocore
Sofia
S
Laboratory of Experimental Immunology, Université Libre de Bruxelles, Belgium.
Paulart
Frédéric
F
Le Moine
Alain
A
Braun
Michel
M
Salmon
Isabelle
I
Van Meirvenne
Sonja
S
Thielemans
Kris
K
Goldman
Michel
M
Flamand
Véronique
V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000172:deficiency; D012190:Retroviridae / Q000235:genetics; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015848:Interleukin-5; D007519:Isoantigens; D017472:Receptors, Interleukin-1; D019014:fas Receptor; D015847:Interleukin-4; D007371:Interferon-gamma