Characterization of T cell maturity in thymic epithelial cell tumors from BUF/Mna spontaneous thymoma rats and BUF/Mna-Rnu/+ rats showing delayed thymomagenesis.

BUF/Mna rats develop thymomas spontaneously, which histologically mimic human thymomas. Although neoplasms in this rat strain contain a large number of immature lymphocytes, the phenotype has not been sufficiently assessed. We characterized T cell phenotypes in tumors from BUF/Mna rats in the present study. We also analyzed BUF/Mna-Rnu/+ rats, a heterozygous strain with suppressive thymomagenesis, and compared the histology and T cell maturation with those from the BUF/Mna rats. A total of 11 BUF/Mna and 10 BUF/Mna-Rnu/+ rats were used. Three-color flow cytometry was performed with anti-CD3, CD4, and CD8 antibodies to identify infiltrated lymphocytes, while tumor histology was evaluated with hematoxylin-eosin staining. The weight ratios of the entire thymic tissue including thymoma as compared to the BUF/Mna and BUF/Mna-Rnu/+ rat bodies were 0.8+/-0.8% and 1.2+/-1.8%, respectively. Histological findings for both rat congenic strains showed abundant lymphocytes surrounding large polygonal neoplastic thymic epithelia, which was compatible with the type B1 classification of the World Health Organization for human thymoma. CD4+CD8+ T cells accounted for 73.7+/-8.0% of the cells in tumors from BUF/Mna and 67.2+/-9.4% in those from BUF/Mna-Rnu/+ rats. Further, CD3-CD4-CD8+ T cells, intermediate between CD4-CD8-and CD4+CD8+ cells, accounted for 47.7+/-17.5% and 38.0+/-14.0% of the cells in tumors from the BUF/Mna and BUF/Mna-Rnu/+ strains, respectively. Thus, the proportion of developing thymic lymphocytes in and histology of thymomas from BUF/Mna and BUF/Mna-Rnu/+ rats were similar. These results suggest that both BUF/Mna and BUF/ Mna-Rnu/+ strains are suitable animal models for human thymoma to understand the development of immature thymic lymphocytes.