Administration of anti-CD4 monoclonal antibody with intrathymic injection of alloantigen results in rat cardiac allograft tolerance

Surgery. 1995 Aug;118(2):265-72; discussion 272-3. doi: 10.1016/s0039-6060(05)80333-2.


Background: We have previously reported the induction of donor-specific tolerance to cardiac allografts after intrathymic injection of alloantigen with simultaneous administration of antilymphocyte serum treatment to eliminate peripheral T cells. The present study determines whether prolongation of a fully major histocompatibility complex-mismatched cardiac allograft is achieved after a single administration of anti-CD4 monoclonal antibody (MoAb) combined with intrathymic injection of alloantigen.

Methods: Male Buffalo rats were given Lewis splenocytes via the intrathymic or intravenous route in combination with a single administration of anti-CD4 monoclonal antibody (OX-38) or anti-CD8 MoAb (OX-8) or both. Heterotopic cardiac transplantation was performed 21 days after intrathymic alloantigen or MoAb pretreatment or both. Fluorescence-activated cell sorter analysis determined changes in lymphocyte compartment T-cell subsets, and in vitro studies examined recipient cellular reactivity.

Results: By 21 days after anti-CD4 MoAb treatment earlier nonspecific immunosuppression had resolved with 80% recovery of peripheral CD4+ T cells and restoration of recipient immunocompetence to allow normal rejection of a cardiac allograft. Combined treatment with intrathymic, but not intravenous, alloantigen plus anti-CD4 MoAb induced donor-specific tolerance to subsequent rat cardiac allografts. However, anti-CD8 MoAb combined with intrathymic alloantigen failed to induce tolerance despite a profound depletion of the CD8+ T-cell subset.

Conclusions: Combined treatment of rats with intrathymic donor alloantigen and a single administration of anti-CD4, but not anti-CD8, MoAb significantly prolongs cardiac allograft survival across a fully major histocompatibility complex mismatched strain combination.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • CD4 Antigens / immunology*
  • CD4 Lymphocyte Count
  • CD8 Antigens / immunology
  • Heart Transplantation*
  • Immune Tolerance*
  • Injections
  • Isoantigens / administration & dosage*
  • Isoantigens / immunology
  • Male
  • Preoperative Care
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred BUF
  • Rats, Inbred Lew
  • Thymus Gland
  • Transplantation, Homologous


  • Antibodies, Monoclonal
  • CD4 Antigens
  • CD8 Antigens
  • Isoantigens