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Three biweekly infusions of a x 10(10) highly purified LEW (RT1l) erythrocytes (LEW-E) administered to BN (RT1n) rats commencing at 1 month of age failed to elicit alloantibody or cell-mediated cytotoxicity against LEW target cells. The magnitude of the proliferative response of lymphocytes taken from LEW-E-infused BN rats in unilateral mixed lymphocyte culture against LEW stimulator cells was identical to that of control BN lymphocytes. LEW renal grafts inserted in LEW-E-infused BN rats showed a markedly prolonged survival which was specific since Wistar (RT1u) renal allografts were acutely rejected. LEW kidneys grafted to unmodified and LEW-E-infused BN recipients elicited cytotoxic antibody responses to Ia-like antigens and cellular immune responses of identical magnitude and specificity. On the other hand, LEW renal grafts evoked hemagglutinating alloantibody in control BN recipients but failed to do so in LEW-E-infused BN recipients. This unresponsiveness to LEW-E-associated antigens was specific since Wistar renal grafts elicited anti-Wistar hemagglutinin responses in LEW-E-infused BN recipients. These results suggest that antibodies to LEW-E-associated alloantigens play an essential role in the acute rejection of LEW renal grafts by BN recipients.
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