Anti-transferrin receptor monoclonal antibody

A novel immunosuppressant

Jennifer E. Woodward, Allison L Bayer, Kenneth D. Chavin, Kimberly A. Boleza, Prabhakar Baliga

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 languageEnglish
Pages (from-to)6-9
Number of pages4
JournalTransplantation
Volume65
Issue number1
DOIs
StatePublished - Jan 15 1998
Externally publishedYes

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Transferrin Receptors
Immunosuppressive Agents
Monoclonal Antibodies
T-Lymphocytes
Immunosuppression
Allografts
Graft Rejection
Cell Surface Receptors
Cytotoxic T-Lymphocytes
Heart Transplantation
T-Cell Antigen Receptor
Cellular Immunity
Transplantation
Lymphocytes

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 journalArticle

Woodward, Jennifer E. ; Bayer, Allison L ; Chavin, Kenneth D. ; Boleza, Kimberly A. ; Baliga, Prabhakar. / Anti-transferrin receptor monoclonal antibody : A novel immunosuppressant. In: Transplantation. 1998 ; Vol. 65, No. 1. pp. 6-9.
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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.",
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