The capacity of histocompatibility antigens solubilized in hypertonic salt solution to induce allograft tolerance in rats.

Treatment of Fisher rats (AgB 1,26,28) with a soluble extract of histocompatibility antigens (SAE) prepared from the liver of donor August rats (AgB 5, 28, 31) associated with a few injections of anti-lymphocyte serum (ALS) provoked a specific prolongation of the median survival time of skin grafts from 27.6 +/- 11.4 days in ALS-treated controls to 55.1 +/- 8.8 days (p less than 0.01). The SAE was obtained from liver homogenates by hypertonic KCl (3M) extraction. Further purification by chromatography in DEAE-cellulose column resulted in the separation of fractions possessing a specific inhibitory activity on a Fisher anti-August cytotoxic serum that was almost 100 times higher than that of the initial SAE preparation. Analysis of the state of unresponsiveness induced by SAE and ALS showed that most of the unresponsive animals had in their serum blocking factors. On the other hand, in vitro study of proliferative and cytotoxic components of cell-mediated immunity by mixed lymphocyte reaction and cell-mediated lympholysis, respectively, showed that the proliferative reactivity remained unimpaired whereas the cytotoxic reactivity was clearly inhibited in the tested animals. These results suggest that a central tolerance to histocompatibility antigens (equivalent to those coded by the K and D end in the mouse) could have been induced in the experimental animals whereas reactivity to Ia region antigens was not affected.