TY - JOUR
T1 - B cells engineered to express Fas ligand suppress pre-sensitized antigen-specific T cell responses in vivo
AU - Kosiewicz, Michele M.
AU - Krishnan, Anasuya
AU - Worthington, Mark T.
AU - Matriano, James A.
AU - Ross, William G.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Antigen-presenting cell
KW - B cell
KW - Delayed-type hypersensitivity
KW - Fas ligand
KW - Immunosuppression
UR - http://www.scopus.com/inward/record.url?scp=0036080346&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036080346&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(200206)32:6<1679::AID-IMMU1679>3.0.CO;2-5
DO - 10.1002/1521-4141(200206)32:6<1679::AID-IMMU1679>3.0.CO;2-5
M3 - Article
C2 - 12115651
AN - SCOPUS:0036080346
SN - 0014-2980
VL - 32
SP - 1679
EP - 1687
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -