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The spleens of rats were studied by light and electron microscopy during the course of an acute myelogenous leukemia, with special reference to infiltration of leukemic myeloblasts in the spleens and to the correlation of leukemic cell infiltration with splenic hematopoiesis and splenomegaly. Leukemic myeloblasts infiltrated the cordal space of the red pulp. Many of them appeared in groups. Even in spleens which were heavily infiltrated, leukemic myeloblasts did not penetrate the while pulp. Massive infiltration and proliferation of the leukemic myeloblasts in the red pulp resulted in splenomegaly. The spleen increased its hematopoietic activity, while the medullary hematopoiesis diminished due to the invasion of leukemic myeloblasts in the bone marrow. Compensatory splenic hematopoiesis occurred in most of the leukemic spleens, but diminished in spleens which were very heavily infiltrated with leukemic myeloblasts. Thus, the degree of splenomegaly and splenic hematopoiesis did not necessarily correspond to the percentage of leukemic myeloblasts in the bone marrow, but rather related to the number of leukemic myeloblasts present in the spleen. A possible role for the splenic sinus walls in promoting compensatory hematopoiesis in the spleen is discussed. A consistent association of type "C" virus particles with leukemic myeloblasts was observed.

Previous studies have shown that multiple transfusions of spleen cells from histocompatible nondiabetic donors prevent autoimmune diabetes mellitus in diabetes-prone (DP) BioBreeding/Worcester (BB/Wor) rats. In this study, a single transfusion of greater than or equal to 50 x 10(6) cells from either diabetes-resistant (DR) BB/Wor or Wistar-Furth (WF) rats substantially reduced the incidence of diabetes when given to DP rats 27 or 46 days old but not 61 days old. Transfusion and protection were associated with the appearance of RT6+ donor lymph node cells in recipient rats. In vivo depletion of RT6+ T-lymphocytes in 150-day-old protected animals did not produce diabetes. DR BB/Wor and WF spleen cells were equally efficacious when given either intraperitoneally or intravenously. Mitogen-activated spleen cells were relatively less effective than untreated cells. We conclude that BB rat diabetes can be prevented by one transfusion of spleen cells from histocompatible DR and WF donors, and that the protective effect is dependent on recipient age and cell dose. The effect may be mediated by a population of RT6+ T-lymphocytes that, during a critical developmental period, regulate the expression of autoimmunity in these animals.

Injections of media conditioned by concanavalin A-activated spleen cells from acutely diabetic rats accelerated the appearance of diabetes in young Bio-Breeding/Worcester (BB/W) rats. Activity was also found in media conditioned by spleen cells from nondiabetic, W-line Wistar Furth and Buffalo rats. Unconditioned media containing mitogen had no activity. Conditioned media also induced diabetes in resistant W-line BB/W rats but not in Wistar Furth rats. A soluble factor may activate a BB lymphocyte population that promotes diabetes.

We report that transfusions of RT1u Wistar-Furth (WF) spleen cells prevented spontaneous diabetes in the RT1u BB/W rat while RT1b Buffalo rat spleen cells did not. In addition, donor origin WF T lymphocytes were detected in nondiabetic-susceptible BB/W recipients 5 mo after transfusion. Survival of donor-origin lymphocytes may provide the cellular mechanism by which major histocompatibility complex-compatible WF spleen cell transfusions prevent BB rat diabetes.