EXPRESSION OF LIF IN TRANSGENIC MICE RESULTS IN ALTERED THYMIC EPITHELIUM AND APPARENT INTERCONVERSION OF THYMIC AND LYMPH-NODE MORPHOLOGIES

Leukemia inhibitory factor (LIF) is a cytokine involved in embryonic a nd hematopoietic development. To investigate the effects of LIF on the lymphoid system, we generated a line of transgenic mice that expresse s diffusible LIF protein specifically in T cells. These mice display t wo categories of phenotype that were not previously attributed to LIF overexpression. First, they display B cell hyperplasia, polyclonal hyp ergammaglobulinemia and mesangial proliferative glomerulonephritis, de fects similar to those described for transgenic mice overexpressing th e functionally related cytokine, interleukin-6. Secondly, the LIF tran sgenic mice display novel thymic and lymph node abnormalities. In the thymus, cortical CD4+CD8+ lymphocytes are lost, while numerous B cell follicles develop. Peripheral lymph nodes contain a vastly expanded CD 4+CD8+ lymphocyte population. Furthermore, the thymic epithelium is pr ofoundly disorganized, suggesting that disruption of stroma-lymphocyte interactions is responsible for many observed defects. Transplantatio n of transgenic bone marrow into wild type recipients transfers both t he thymic and lymph node defects. However, transplantation of wild typ e marrow into transgenic recipients rescues the lymph node abnormality , but not the thymic defect, indicating the thymic epithelium is irrev ersibly altered. Our observations are consistent with a role for LIF i n maintaining a functional thymic epithelium that will support proper T cell maturation.