Abstract
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 ζ-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 (H2(k)) 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 anti-transferrin receptor mAb.
| Original language | English |
|---|---|
| Pages (from-to) | 6-9 |
| Number of pages | 4 |
| Journal | Transplantation |
| Volume | 65 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 15 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Transplantation
- Immunology
Cite this
Anti-transferrin receptor monoclonal antibody : A novel immunosuppressant. / Woodward, Jennifer E.; Bayer, Allison L; Chavin, Kenneth D.; Boleza, Kimberly A.; Baliga, Prabhakar.
In: Transplantation, Vol. 65, No. 1, 15.01.1998, p. 6-9.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-transferrin receptor monoclonal antibody
T2 - A novel immunosuppressant
AU - Woodward, Jennifer E.
AU - Bayer, Allison L
AU - Chavin, Kenneth D.
AU - Boleza, Kimberly A.
AU - Baliga, Prabhakar
PY - 1998/1/15
Y1 - 1998/1/15
N2 - 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 ζ-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 (H2(k)) 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 anti-transferrin receptor mAb.
AB - 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 ζ-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 (H2(k)) 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 anti-transferrin receptor mAb.
UR - http://www.scopus.com/inward/record.url?scp=0031936264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031936264&partnerID=8YFLogxK
U2 - 10.1097/00007890-199801150-00003
DO - 10.1097/00007890-199801150-00003
M3 - Article
VL - 65
SP - 6
EP - 9
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 1
ER -