Abstract
Treatment with a pyrimidine nucleoside, cytarabine, combined with ALS, resulted in greatly prolonged survival of histoincompatible rat skin allografts in comparison with ALS or cytarabine used alone. Depending upon the potency of the ALS, 20% to 65% of the rats tolerated grafts for greater than 100 days despite the fact that treatment was limited to daily nontoxic doses of ALS and cytarabine given for only 10 and 22 days, respectively. With the same finite treatment, significant improvement of graft survival as compared with ALS given alone was achieved in sensitized animals, and in mouse-to-rat skin xenografts (31-day median survival). In the latter two cases, however, no animal permanently retained its graft. The possible mechanisms of the synergism of these two agents were discussed, and it was tentatively concluded that either concomitant suppression of both humoral and cellular responses or total suppression of the cellular response was responsible. Preliminary examination of the grafted animals indicated that graft survival was not due to specific immunologic tolerance to donor antigens and probably not to enhancement. It was tentatively concluded that “adaptation” of the grafts had occurred.
