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We investigated the sensitivity of thyroid epithelial cells (thyrocytes) to IL-2 activated killer cells. The thyrocytes were lysed by autologous and allogeneic IL-2-activated killer cells; there were no differences in sensitivity to the killer cells between normal thyrocytes and thyrocytes from patients with Graves' disease. When thyrocytes were pretreated with recombinant interferon (rIFN) gamma or alpha, the IL-2-activated killer cell-mediated cytotoxicity was depressed and varied inversely with the cell surface expression of class I HLA gene products. The rIFN-gamma pretreatment did not alter the kinetics of thyrocytes lysis by IL-2-activated killer cells. Using cold target competition analysis, rIFN-gamma-pretreated thyrocytes clearly competed less effectively than did untreated cells for lysis of untreated target cells. These results suggest that rIFN-gamma or IFN-alpha pretreatment of thyrocytes may reduce their ability to be recognized by effector cells. These findings suggest that destruction of thyrocytes in autoimmune thyroiditis may be, in part, due to IL-2-activated killer cells and may be regulated by IFN.

Radiation-induced L8313 leukemia bearing mice (L8313 mice) had marked granulocytosis with splenomegaly. Hemopoietic stem cells and progenitors increased in the spleen but not in the bone marrow. Spleen conditioned-medium and serum from L8313 mice induced the formation of granulocyte-macrophage colonies (CFU-GM), erythroid bursts (BFU-E) and mixed colonies (CFU-Mix). Bone marrow conditioned medium did not show such activity. A cell line (STIL-3) was established from the spleen cells of L8313 mice. Surface marker analysis showed that the established cells were suppressor T cell. The cells produced IL-3 and GM-CSF in vitro, and induce essentially the same "leukemic" response in recipient mice. Inoculation of STIL-3 in diffusion chamber also induced leukemoid reaction, i.e. a marked granulocytosis with splenomegaly. Therefore, L8313 leukemia may be linked to an abnormality of growth and production of hemopoietic factors in hemopoietic regulatory cells.

The colony-stimulating factor-producing BMA-1 tumor was transplanted into splenectomized mice. These mice showed as much granulocytosis as non-splenectomized mice bearing the tumor. The increase in the number of peripheral leukocytes induced per tumor weight was similar in the two groups. The hemopoietic cell population in the central bone marrow (tibia) was not increased by splenectomy. The total numbers of spleen colony-forming cells and granulocyte-macrophage colony-forming cells in the whole body of tumor-bearing splenectomized mice were 29% and 58% of those in the tumor-bearing non-splenectomized mice, respectively. The expansion of hemopoiesis to the peripheral bone marrow in tumor-bearing splenectomized mice was confirmed by histological examination of the tail bone. These results suggest that the lack of increase in the bone marrow cellularity is due to the space limitation, and that this is well compensated for by a great expansion of hemopoietic marrow to the peripheral bones in splenectomized mice.