Inhibition of allograft rejection by anti-T-cell receptor-αβ monoclonal antibodies preserving resistance to bacterial infection

M. Eto, Y. Yoshikai, Y. Nishimura, K. Hiromatsu, T. Maeda, K. Nomoto, Y. Y. Kong -, R. T. Kubo, J. Kumazawa, K. Nomoto

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Anti-CD3 monoclonal antibody (mAb) has been administered in clinical organ transplantation to reverse acute allograft rejection; however, severe immunodeficiency can result from such mAb treatment and cause an increased incidence of opportunistic infections. Therefore, new model systems are required in order to establish better methods for suppressing allograft rejection while preserving resistance to opportunistic infections. In this study, we compared the effects of the in vivo administration of anti-T-cell receptor-αβ (TcRαβ) mAb, H57-597, with those of anti-CD3 mAb, 145-2C11. Much to our surprise, the in vivo administration of anti-TcRαβ mAb prior to skin grafting led to a longer allograft survival than that of anti-CD3 mAb at any of the comparable dosages examined. In the lymphoid organs of mice treated with anti-TcRαβ mAb, TcRαβ-bearing cells were almost completely depleted, while TcRγδ-bearing cells remained at a relatively increased level on day 14 after anti-TcRαβ mAb treatment. The in vitro stimulation by anti-TcRγδ mAb clearly showed that such TcRγδ-bearing cells were functionally intact. Furthermore, the mice treated with anti-TcRαβ mAb, but not anti-CD3 mAb, were observed to be resistant to infection with Listeria monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a marked prolongation of skin allograft survival in the thymectomized mice. These results strongly suggest that anti-TcRαβ mAb, which partially preserved anti-bacterial resistance, may be more effective in preventing graft rejection than anti-CD3 mAb in the periphery, and indicate that anti- TcRαβ mAb may thus be potentially applicable for human transplantation. In addition, these results also indicate that the TcRαβ-bearing cells alone, at least in the absence of TcRαβ-bearing cells, do not contribute to allograft rejection in vivo.

Original languageEnglish
Pages (from-to)198-204
Number of pages7
JournalImmunology
Volume81
Issue number2
Publication statusPublished - 1994

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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