The morphologic responses of the lymphoid system to homografts. II. The effects of antimetabolites.

I N A PREVIOUS paper, the morphology of the lymphoid system of the rabbit during the development of transplantation immunity was described.1 The outstanding feature of the reaction was the proliferation of primitive cells ( hemocytoblasts ), which, although they first appeared in the lymph node contiguous to the graft, were eventually seen throughout the entire lymphatic apparatus of the animal. The growth of hemocytoblasts was associated with enlargement of the germinal centers and lymphoid follicles of the lymph nodes and spleen, and with effacement of normal landmarks. Although these lymphoid changes were most prominent at the peak of the reaction within the graft, they persisted for many days, especially after the rejection of a second set graft. The results of this study were considered to be consistent with the concept that immunity to a local graft eventually becomes a generalized reaclion. They also suggested that a second set phenomenon may represent an anamnestic response, rather than a state of sustained immunity, which is “revealed” by the second graft. The present report describes the effects of the antimetabolites 6-mercaptopurme ( 6-MP ) and thioguanine on these responses. It was found that these agents abolished the cellular proliferation described above; for as long as the growth of hemocytoblasts was prevented by the drugs, the homograft reaction did not occur. On the other hand, permanent suppression of the homograft reaction did not occur. Graft rejection despite the continued administration of 6-MP was marked by an explosive proliferation of hemocytoblasts and a striking hyperplasia of the germinal centers and follicles of the lymph nodes and spleen. The hemocytoblasts which appeared in these rabbits were considered to be “drug resistant” and analogous to resistant bacterial or leukemic cell populations which thrive despite the continued presence of antimetabolites.