Induction of tolerance to heart allografts in high responder rats by combining anti-CD4 with CTLA4Ig.

Yin D, Fathman CG
J Immunol. 1995 155 (4): 1655-9

PMID: 7636225

It has been difficult to induce donor-specific transplantation tolerance in high responder Lewis rats. Results presented below demonstrate that amounts of pretransplant anti-CD4 sufficient to allow allograft tolerance in low responder strains (5 mg/kg x 4 days) did not prevent the acute rejection of ACI heart allografts in high responder Lewis recipients. Higher doses of pretransplant anti-CD4 (10 mg/kg, 15 mg/kg, and 20 mg/kg) given alone could delay but not prevent allograft rejection. Pretransplant anti-CD4 combined with anti-CD8, thymectomy, and total lymphoid irradiation all failed to produce tolerance to ACI heart allografts. However, a regimen of anti-CD4 combined with CTLA4Ig allowed indefinite survival of ACI heart allografts (mean survival time, > 100 day). Second-donor matched heart grafts were permanently accepted, and third-party heart grafts were permanently accepted, and third-party heart allografts were rejected by the tolerant recipients. These results suggest a new combination therapeutic strategy for clinical transplantation.

MeSH Terms (17)

Abatacept Animals Antibodies, Monoclonal Antigens, CD Antigens, Differentiation CD4 Antigens CTLA-4 Antigen Graft Survival Heart Transplantation Immune Tolerance Immunoconjugates Male Mice Rats Rats, Inbred ACI Rats, Inbred Lew Transplantation, Homologous

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