Selective T-cell depletion with Ox-38 anti-CD4 monoclonal antibody prevents cardiac allograft rejection in rats.
New monoclonal antibodies directed to membrane molecules unique to lymphocyte subsets have provided the means to alter the immune response to alloantigens in a more selective fashion. This investigation demonstrates that monoclonal antibody-induced depletion of CD4 helper/inducer T lymphocytes before transplantation of a fully mismatched heart allograft allows permanent engraftment in rats without further immunosuppression. Five adult male ACI (RT1a) rats received cell-depleting doses of the mouse anti-rat CD4 monoclonal antibody, MRC Ox-38, for 1 month before undergoing heterotopic abdominal heart transplantation. No other immunosuppression was administered, and immunotherapy was discontinued the day of transplantation. After all five Lewis rat (RT1(1)) hearts were maintained free of rejection for more than 3 months, a second heterotopic transplant was performed, this time to the femoral vessels, using either fresh Lewis heart allografts (n = 3) or third-party, Brown-Norway (RT1n) hearts (n = 2). Histologic evaluation was performed 3 weeks later and revealed severe rejection of the femoral Brown-Norway grafts with no evidence of rejection in any of the femoral or original abdominal Lewis grafts. These results suggested that limited, pretransplant anti-CD4 immunotherapy allowed permanent engraftment of fully mismatched cardiac allografts in rats and conferred donor-specific unresponsiveness.
Flavin
T
T
Division of Cardiothoracic Surgery, University of Iowa Hospitals and Clinics, Iowa City.
Shizuru
J
J
Seydel
K
K
Wu
A
A
Fujimoto
N
N
Hoyt
E G
EG
Ivens
K
K
Billingham
M
M
Fathman
C G
CG
Starnes
V A
VA
D000005:Abdomen; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005263:Femoral Artery; D005268:Femoral Vein; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016042:Transplantation, Heterotopic
D000911:Antibodies, Monoclonal