ion o f a Specific Suppressor Cell

The mechanisms that allow the long-term survival of major histocompatibility complex (MHC)Limmunologically enhanced organ allografts are poorly understood (1-5). In rodents, enhancement can be induced by treatment with either hyperimmune serum at the time of grafting or prior immunization with donor ailoantigen. After a treatment rejection episode, many of these rats develop a state in which the immune system capacity of the host to develop a rejection response is specifically inhibited (1-5). Specific unresponsiveness to donor strain alloantigen in animals with established enhanced grafts is manifested by an inability to reject directly vascularized organ grafts from a second donor strain, but a normal capacity to reject third party grafts (3-6). Also, in rats with enhanced grafts, the rejection of donor strain but not third party skin grafts, is delayed and the length of the delay is inversely related to the time after grafting (7). This suggests that these animals have a specific inhibitory response that matures with time. Although the induction of enhancement is antibody mediated, attempts to demonstrate humoral mediators during the maintenance phase of enhancement have been unsuccessful. After passive enhancement, grafts survive long after the injected antibody has been metabolized, and in recipients with actively enhanced grafts, the alloantibody titers wane after the first month (3, 8). Serum from rats with enhanced grafts will not enhance graft survival in a second host, and attempts to identify antiidiotype or blocking antibodies in the serum have mostly been unsuccessful (2, 9-12). Attempts to identify the cellular basis of this inhibitory response, which maintains prolonged graft survival, have thus far failed to demonstrate a suppressor cell mechanism. Hendry et al. (13) demonstrated a specific suppressor cell in thymus and spleen of rats during the induction phase of enhancement, but this effect, which could be transferred to nonimmunosuppressed rats, waned with time and was not demonstrated in the maintenance phase. Fabre and Morris (9) adoptively transferred spleen cells from rats bearing enhanced kidney allografts to normal rats grafted with kidney allografts, but they failed to transfer enhancement. Batchelor et al. (14) also failed to adoptively This work was supported by the Medical Research Council of Canada. Address correspondence to Dr. Bruce M. Hall, Dept. of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, 2050, N.S.W., Australia. ~Abbreviations used in this paper: ALG, antilymphocyte globulin; GVH, graft-vs.-host; LNC, lymph node cells; MHC major histocompatibility complex; MLC, mixed lymphocyte culture.