Reduced immunogenicity of long-term, passively enhanced rat renal allografts and passive transfer of graft protection

Abstract

Enhancing alloantiserum was produced by immunizing male BD IX inbred rats with density gradient separated nylon-wool adherent spleen lymphocytes from male rats of the major histocompatibility complex (MHC) different inbred strain Sprague-Dawley (SD). Long-term surviving (BD IX × SD) F1 to BD IX kidney grafts were achieved by treating the recipients with 1 ml alloantiserum at the time of transplantation. After >100 days 7 passively enhanced F1 kidneys were retransplanted into naive BD IX rats. Four out of 7 secondary recipients, producing only low levels of lymphocytotoxic antibodies, survived for >100 days, 3/7 rats died of surgical or infection complications. Twenty-one naive BD IX recipients of normal F1 kidneys were treated with serum (1 ml i.v.) and/or spleen lymphocytes (1 × 10 7 i.v.) obtained from the longterm survivors. An indefinite graft survival was achieved in 13 out of 21 rats. After >150 days 6 out of these 13 passively enhanced F1 kidneys were retransplanted into naive BD IX rats which were challenged at the time of grafting with 4×10 7 SD lymphocytes to elicit rejection. Six out of 6 kidneys survived >150 days. Thus, the longterm survival of rat kidney allografts in this model is associated with a strong reduction of graft immunogenicity as well as the development of suppressor cells and enhancing antibodies.