Increased survival of vascularized organ allografts in the rat has been achieved by active host immunization with donor antigen, passive immunization with alloantise-

Increased survival of vascularized organ allografts in the rat has been achieved by active host immunization with donor antigen, passive immunization with alloantiserum, and a combination of both (1-5). The original concept, as suggested by Kaliss, that immunological enhancement is mediated by host humoral factors, is still widely held, although the exact mechanisms involved in its initiation and maintenance remain unresolved (6). However, passive transfer of serum from enhanced animals rarely increases survival of test aliografts, despite detection of humoral blocking factors in some enhancement models (7). The contributions to allograft enhancement by the cellular-immune responses have not been rigorously assessed, although evidence for in vivo activity of cells capable of causing specific unresponsiveness has been found in other animal systems: for example, host responses against tumors may be influenced by cells or cellular products (8-10), which also act in delayed hypersensitivity (11-13) and graft-versus-host reactions (14-16). In studies of transplantation tolerance, induced neonatally, suppressor cells have been demonstrated primarily to be recirculating T cells which show specificity in vivo to donor strain tissues (17, 18). We have shown previously that spleen cells and infiltrating leukocytes isolated from well-functioning cardiac allografts in enhanced adult rats suppress spontaneous blastogenesis of normal syngeneic cells in vitro (19). Additionally, preliminary observations in vivo have suggested that lymphoid cells from enhanced animals bearing a well-functioning organ aUograft are able to transfer a state of specific unresponsiveness to unmodified recipients (20). The present studies demonstrate the precise activity of thymocytes in the early phase of immunological enhancement, confirm the specificity of this effect, and describe the necessity of an intact thymus for continued survival of the grafted organ in an enhanced host. Our observations suggest that the phenomenon of enhancement of organ atlografts induced by particular immunizing protocols, involves cellular as well as humoral mechanisms.