Lorraine Beldotti

Malignant Lymphomas Following Allogenic Disease: Transition from an Immunological to a Neoplastic Disorder

The graft versus host reaction which occurs in F1 hybrid mice injected with parental spleen cells was used to examine several immunological theories of neoplasia. Long-term survivors of this reaction developed lymphoid neoplasms which resembled Hodgkins disease and lymphosarcoma. Mice with these tumors were chimeras, but the parental cells present within their spleens had specific immunological tolerance toward host antigens. This, together with the finding that the tumors were transplantable only to isogenic recipients, indicates that the tumors were of host rather than donor origin.

Neoplastic sequelae of allogeneic disease. Iii. Histological events following transplantation of allogeneic spleen cells.

(C57BL/6 X DBA/2) F1 hybrid mice injected at the age of 6 weeks with C57BL/6 spleen cells were killed at regular intervals from 1 week to 15 months after the administration of parental cells and their tissues were examined histologically. The earliest changes in the spleen and lymph nodes consisted of proliferation of large mono-nuclear cells, together with varying degrees of small lymphocyte depletion. Thereafter, three types of abnormalities of the lymphoid tissue were found: (1) atrophy, (2) expansion of lymph follicles into irregular masses of pleomorphic cells, (3) replacement of lymph follicles by histiocytes. The latter two lesions are thought to represent the antecedents of the malignant lymphomas which may develop in the long-term survivors of the graft-versus-host reaction. These findings support the concept that the transition from an immunological disorder, allogeneic disease, to a malignant growth is part of a continuous process initiated by the transplantation of foreign lymphoid cells. Thymic atrophy was not a feature in the present parent-hybrid combination, suggesting that the manifestations of the graft-versus-host reaction are not necessarily dependent on thymic destruction.

THE TREATMENT OF CHRONIC MURINE HOMOLOGOUS DISEASE: A COMPARATIVE STUDY OF FOUR "IMMUNOSUPPRESSIVE" AGENTS.

Treatment of chronic homologous disease, induced in young adult (C57BL/6 X DBA/2)F1 mice by injections of C57BL/6 spleen cells, was attempted with four agents: 6-mercaptopurine (6-MP), prednisone, methotrexate and total body X-radiation. 6-MP caused acceleration of the disease, regardless of dosage or timing of administration. Prednisone ameliorated homologous disease only when given at the same time as the parental cells. Methotrexate treatment suppressed the disease only when given after the parental cells, at a time when active disease is ordinarily expected. Total body X-radiation (400 r) led to extreme susceptibility to the graft-versus-host reaction, even if given 2 weeks before or 60 days after the parental cells. However, a period approximately 3 weeks after administration of parental cells was radioresistant in that no acceleration of the disease occurred. The accelerating effect of 6-mercaptopurine could not be reversed by administering isologous spleen cells. Amelioration of homologous disease by methotrexate was associated with the acquisition of durable specific immunological tolerance of host antigens by the injected parental cells.