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  • Title: Anti-CD4 therapy in combined heart-kidney, heart-liver, and heart-small bowel allotransplants in high-responder rats.
    Author: Yin DP, Sankary HN, Talor-Edwards C, Chong AS, Foster P, Shen J, Ma LL, Williams JW, Fathman CG.
    Journal: Transplantation; 1998 Jul 15; 66(1):1-5. PubMed ID: 9679814.
    Abstract:
    BACKGROUND: In these experiments, we studied the role of anti-CD4 (Ox38) monoclonal antibody in the induction of allograft unresponsiveness in high-responder Lewis rats in the single liver, kidney, small bowel, and heart versus the combined heart-kidney, heart-liver, and heart-small bowel transplantation models. METHODS: ACI heart, kidney, liver, and small bowel allografts were transplanted into untreated and anti-CD4 treated Lewis rats. In selected animals bearing long-surviving ACI liver or kidney allografts for over 3 months, donor-matched second heart or third-party (Brown Norway) heart allografts were transplanted. Simultaneously, heart-liver, heart-kidney, and heart-small bowel transplants were performed on the day of operation. Rejected allografts were verified by autopsy and pathology. RESULTS: ACI liver allografts were permanently accepted by Lewis recipients treated with either regular-dose (5 mg/kg for 4 days) or low-dose (5 mg/kg for 2 days) of anti-CD4 monoclonal antibody. Pretransplant anti-CD4 therapy (5 mg/kg for 4 days but not 5 mg/kg for 2 days) resulted in a long-term survival of kidney allografts (mean survival time [MST] > 100.0 days, n=5). Pretransplant anti-CD4 treatment (5 mg/kg for 4 days) could not induce tolerance when single ACI hearts were transplanted; however, long-term survival of ACI heart allografts could be induced when heart transplants were combined with liver (n=7) or kidney (n=8) transplants. The survival of both ACI heart allografts (MST=25.0 days, n=4) and small bowel allografts (MST=28.0 days, n=4) was also prolonged when simultaneous heart and small bowel transplantation was performed in anti-CD4-treated recipients. The second ACI heart allograft was permanently accepted by tolerant Lewis recipients of ACI liver or kidney allografts induced by anti-CD4 treatment, and third-party heart grafts were acutely rejected without affecting survival of the primary allografts. CONCLUSION: Our current results show that: (1) there is a vigorous rejection of heart > or = small bowel > kidney > liver in high-responder Lewis rats after pretransplant anti-CD4 therapy; and (2) simultaneous or metachronous combined liver-heart and kidney-heart transplants may protect heart allografts from rejection.
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