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Ligature of the cervical lymph duct in guinea pigs resulted in marked dilatation of the lymphatics draining the thymus and marked reduction of mitosis in the thymus. A decrease of about 50% in the number of mitoses was found in the cortex within one day after ligation and in the medulla within five days after ligation. The thickness of the cortex also decreased rapidly and markedly in direct proportion to the decrease in cortical mitosis. Mitosis in the thymus recovered within 10 days after ligation, presumably after regeneration of lymphatics or collateralization. Thickening of the walls and valves of the efferent lymphatics of the thymus after lymph congestion was also demonstrated.

We examined the possible relationship between thymic mast cells and increased vascular permeability in the thymus of autoimmune NZB/W F1 mice. Light-microscopic observation of tissue sections showed that non-autoimmune BDF1 mast cells increased with age. In contrast, autoimmune NZB/W F1 mast cells did not increase in the thymic parenchyma at the age of 9 weeks. However, NZB/W F1 mast cells resumed the age-associated increase from the age of 12 weeks and exceeded the number of BDF1 mast cells at the age of 30 weeks. Blood histamine levels of 9-week-old NZB/W F1 mice were higher than those of BDF1 mice of comparable age. Furthermore, peritoneal mast cells of NZB/W F1 mice were more sensitive to compound 48/80 than those of BDF1 mice. Increased blood histamine levels of NZB/W F1 mice seem to be due to the enhanced histamine release from mast cells. These results suggest a possible correlation between the high histamine levels by degranulation of mast cells and increased vascular permeability in the thymus of NZB/W F1 mice.

General and histochemical observations of the thymus were carried out in guinea pigs after injection of cyclophosphamide (280 mg/kg). Acute involution of the thymus induced by cyclophosphamide was accompanied by marked enlargement of Hassall's corpuscles in the first week after injection. However, the markedly enlarged Hassall's corpuscles disappeared entirely by the fourth week. Large cells characterized by pale nuclei with one or two prominent nucleoli became aggregated in the enlarged Hassall's corpuscles by the second week. Their cytoplasm frequently was foamy or vesicular in appearance. Histochemical observations revealed strong activities of nonspecific esterase, acid phosphatase and beta-glucuronidase in these cells. Staining for these lysosomal hydrolytic enzymes was evident not only intracellularly but also extracellularly, indicating the dissolution of Hassall's corpuscles by intensive extracellular enzyme release.

In order to elucidate possible roles of thymic nurse cells (TNC) we isolated them as lympho-epithelial cell complexes from spontaneous thymomas of BUF/Mna rats and characterized them using immuno- and enzyme-histochemical techniques. A remarkable increase in the number of TNC was seen at 8 months of age, immediately before or in accordance with the onset of thymomas. No structural abnormality in the TNC was detected by light-microscopy compared with those from normal control thymi. Phenotypically, the TNC per se were positive for major histocompatibility complex (MHC) class I, class II, cytokeratin and thymulin, but lacked macrophage markers, indicating their epithelial origin. They also expressed some of the markers for non-epithelial components, such as Thy-1, S100 and peanut agglutinin (PNA). The majority of intra-TNC cells were MHC class 1+, Thy-1+, CD5+, CD4+ CD8+ (double positive) and PNA+, but with some heterogeneity in their phenotype. The intra-TNC cells from thymomas revealed higher proliferation indices than those from control thymi, as assessed by 5-bromo-2'-deoxyuridine (BrdU)-uptake. It was also demonstrated for the first time that, not only in thymoma rats but also in normal control rats, about 15-30% of TNC enclosed macrophage populations within them. These results may suggest that the TNC in BUF/Mna thymomas represent typical TNC populations, but they are hyperactive particularly in their number and nursing capacity, resulting in the unusual increment of thymocytes in the thymomas. This animal model lends itself greatly to studies on the regulatory roles of TNC in T-cell development.

Various amounts of the bacterium, Brucella abortus (BA) were injected intravenously into autoimmune NZB/W F1 mice and non-autoimmune BDF1 mice and then the localization of BA in the thymus was traced using an immunohistochemical method at 30 min and 3 h after injection. The results showed that a greater amount of BA became consistently localized in the thymic parenchyma in a free form or in a phagocytized form in NZB/W F1 mice in comparison with BDF1 mice, indicating a marked increase of vascular permeability in the thymus of NZB/W F1 mice. The extravascular leakage of BA was clearly dose-dependent. The significance of invasion of bacterial antigens from the general circulation into the thymic parenchyma is discussed in relation to autoimmune states.

The thymus glands of non-autoimmune BDF1 and C3H mice and autoimmune NZB/WF1 mice were studied histologically at intervals ranging from one hour to 60 days after systemic administration of carbon. In NZB/WF1 mice over 9 weeks of age, many circulating carbon-laden macrophages were seen to have penetrated the walls of blood vessels, and to have then entered the thymic parenchyma. Carbon was also taken up by many perivascular macrophages stretched out along blood vessels and by many resident tissue macrophages scattered throughout the thymic parenchyma. In contrast, no carbon was seen at any time in the extravascular tissues of the thymus in BDF1 and C3H mice of comparable age. These results indicate a great increase in the permeability of blood vessels in the thymus of NZB/WF1 mice. This increase in carbon permeability occurs both in the cortex and the medulla, particularly at the corticomedullary junction. There is little increase in the permeability to carbon in NZB/WF1 mice at the age of 4 weeks, suggesting that the increase in vascular permeability begins between the ages of 4 and 9 weeks. The possible role of this greatly increased blood vessel permeability in the thymus on the aetiology and pathogenesis of autoimmune disease is discussed.

Various doses of estriol (E3) were given to mice intraperitoneally, immediately after lethal irradiation and marrow reconstitution. The assessment of the plaque-forming cell (PFC) response to sheep erythrocytes in the spleen and the histological assessment of lymphoid tissues were carried out 30 days later. The effects appeared to be dose-dependent and resulted in a marked suppression of the PFC response. The depletion of lymphocytes was dramatic and dose-dependent in the thymus, and in the thymus-dependent and in the thymus independent areas of the peripheral lymphoid tissues. These results suggest that E3 acts on the differentiation of stem or precursor cells toweard both the populations of T and B lymphocytes. Although E3, given on day 7 after irradiation and marrow reconstitution, suppressed the lymphoid regeneration and PFC response markedly, E3 given on day 14 had no effect. On day 7 the majority of regenerating lymphoid tissues were large pyroninophilic cells and on day 14, small lymphocytes. These results suggest that the precursor or immature lymphocytes are sensitive to E3, while mature lymphocytes are resistant. Lymphoid regeneration and PFC response were retarded in mice irradiated and reconstituted with bone marrow cells from donors pretreated with E3. These results suggest that E3 acts on the stem or precursor cells capable to differentiate in the direction of lymphoid populations and reduce their number in the bone marrow.

The dissolution of Hassall's corpuscles by macrophages has been demonstrated in the sheep thymus. The findings indicate that enlarged Hassall's corpuscles are rapidly broken down by macrophages at the end of gestation or immediately after birth and replaced by newly formed corpuscles, and that these cyclic changes in Hassall's corpuscles persist, under normal physiological conditions, throughout life.

Rats of inbred DA strain were given 20 intraperitoneal injections of typhoid-paratyphoid bacilli at 10 day intervals. Thymic lymph follicles with germinal centres were formed in females but not in males. However, orchidectomy permitted the formation of large numbers of thymic lymph follicles with germinal centres in males. The formation of lymph follicles with germinal centres in the thymus was not affected by ovariectomy. These results would appear to suggest an inhibitory role of androgens on the formation of thymic lymph follicles with germinal centres. In addition, large numbers of plasma cells, mast cells, and reticular cells, or macrophages with haemosiderin in their cytoplasm, appeared in the parenchma of the thymus in close association with the formation of thymic germinal centres.