B cells engineered to express Fas ligand suppress pre-sensitized antigen-specific T cell responses in vivo.
Inducing apoptosis of activated lymphocytes via Fas ligand (FasL, CD95) may be a useful strategy for the treatment of autoimmune diseases mediated by pathogenic T cells. We propose that B cells may be ideal tools for effective delivery of a FasL-mediated apoptotic signal to pathogenic T cells for a variety of reasons, including their unique ability to efficiently take up and present antigen to T cells that share the same specificity. Here, we demonstrate that B cell clones engineered to express CD95 can effectively suppress a systemic primed antigen-specific T cell response in vivo. Intravenous injection of antigen-pulsed FasL-expressing B cells eliminated antigen-specific (TCR transgenic) T cells from the draining lymph nodes within 12-60 h, and suppressed a delayed-type hypersensitivity response in an antigen-specific manner. These results indicate that B cells can be engineered to express FasL, and used to impair T cell function in vivo, suggesting that FasL-expressing B cells may be an effective tool for the treatment of established T cell-mediated autoimmune and inflammatory diseases.
Kosiewicz
Michele M
MM
Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA. mmkosi01@gwise.louisville.edu
Krishnan
Anasuya
A
Worthington
Mark T
MT
Matriano
James A
JA
Ross
William G
WG
D000818:Animals; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000628:therapy; D001402:B-Lymphocytes / Q000502:physiology*; D053222:Fas Ligand Protein; D005260:Female; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007165:Immunosuppression Therapy; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000941:Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins