Administration of anti-CD4 monoclonal antibody with intrathymic injection of alloantigen results in rat cardiac allograft tolerance.
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.
Arima
T
T
Department of Surgery, Washington University School of Medicine, St. Louis, Mo., USA.
Goss
J A
JA
Walp
L A
LA
Flye
M W
MW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D016827:CD8 Antigens / Q000276:immunology; D016027:Heart Transplantation; D007108:Immune Tolerance; D007267:Injections; D007519:Isoantigens / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D011300:Preoperative Care; D051381:Rats; D011912:Rats, Inbred ACI; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D013950:Thymus Gland; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D007519:Isoantigens