Anti-transferrin receptor monoclonal antibody: a novel immunosuppressant.
BACKGROUND
Transferrin receptor is a widely distributed cell surface receptor present on most proliferating and highly specialized quiescent cells. Expression of transferrin receptor on the surface of immune cells is up-regulated during T-cell activation after the interaction of the antigen-MHC with the T cell receptor. The role of transferrin receptor in T-cell activation has not been well-established. Since transferrin receptor is physically associated with the CD3 zeta-chain, blockade of transferrin receptor has the potential to interfere with the T-cell signals important in transplant rejection.


METHODS
Anti-transferrin receptor monoclonal antibody (mAb) was administered in vivo and in vitro to determine whether this agent was effective in prolonging allograft survival and altering cell-mediated immunity.


RESULTS
Using donor C57BL/6J (H2b) hearts transplanted to CBA/J (H2k) recipients, anti-transferrin receptor mAb at the time of transplantation prolonged cardiac allograft mean survival time to 25.7+/-0.9 days compared with untreated (13.3+/-0.6 days, P < 0.05) or isotype-matched (10.7+/-0.4 days, P < 0.05) controls. Anti-transferrin receptor mAb administered in vivo failed to suppress the subsequent allogeneic responses. However, when added to culture, anti-transferrin receptor mAb suppressed the allogeneic cytotoxic T lymphocyte response by 79-100% but not the mixed lymphocyte response.


CONCLUSIONS
These studies are the first to suggest that transferrin receptor is a potential therapeutic target for clinical transplantation. Future studies will determine the most efficacious dose and time for maximal immunosuppression and the mechanisms responsible for the immunosuppression exhibited by antitransferrin receptor mAb.
Woodward
J E
JE
Department of Surgery, Medical University of South Carolina, Charleston, 29425, USA.
Bayer
A L
AL
Chavin
K D
KD
Boleza
K A
KA
Baliga
P
P
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D007111:Immunity, Cellular / Q000187:drug effects; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011990:Receptors, Transferrin / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007519:Isoantigens; D011990:Receptors, Transferrin