INDUCTION OF TUMORS AND AUTOIMMUNE CHANGES IN THYMECTOMIZED MICE

(C57Bl/1xA) F₁ hybrid mice were thymectomized within 24 hours of birth. Similan F₁ mice were set aside as controls. These groups have been observed for more than 22 months. By 4 months, one-third of the thymectomized mice had died of postthymectomy wasting, leaving 77 mice for long-term observation. Thereafter, occasional deaths occurred due to renal disease or wasting but most deaths were due to tumor. There was an increased incidence of lymphomas in the thymectomy group, reaching a cumulative value of 40 per cent (31/77) at 22 months, compared to 8 per cent (12/149) in the controls. Thymectomized mice showed a much higher mortality than normal F₁ controls following transplantation of a syngeneic lymphoma, providing evidence of immunologic deficiency in the post-thymectomy state. Histologic changes in the thymectomized mice included arteritis, endocarditis, myositis, synovitis, cellular infiltration of liver and pancreas, renal papillary necrosis, and lesions of skin, bowel lining, and ureter. Lymphoid tissue alterations were prominent: there was a spectrum of changes, from simple lymphocytic depletion in the thymus dependent areas (uncommon) through hyperplasia of reticulum cells to frank reticulum cell sarcomas. These changes were similar to those observed in the graft-versus-host reaction in F₁ hybrids and support the concept of the development of autoimmune processes in thymectomized mice. The lymphomas appeared to be an escalation from hyperplasia to frank malignancy.

These studies provide strong evidence that immunologic deficiency can result in an increased incidence of tumors, confirming clinical observations of patients following organ transplantation (in the latter situation, multiple exogenous agents obscure the picture). These experiments also confirmed and extended previous clinical and animal studies demonstrating an association of immunologic deficiency, autoimmunity, and lymphomas.

Autoimmune processes could result from the production of antibodies to infectious agents which cross-react with host antigens or from the presence of aberrant cells, which, perhaps as a result of viral infection, are responsible for both the lymphoproliferative and autoimmune phenomena.

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