B cells engineered to express Fas ligand suppress pre-sensitized antigen-specific T cell responses in vivo

✍ Scribed by Michele M. Kosiewicz; Anasuya Krishnan; Mark T. Worthington; James A. Matriano; William G. Ross

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 245 KB
• Volume: 32
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200206)32:6<1679::aid-immu1679>3.0.co;2-5

✦ Synopsis

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.