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 and hematopoietic development. To investigate the effects of LIF on the lymphoid system, we generated a line of transgenic mice that expresses diffusible LIF protein specifically in T cells. These mice display two categories of phenotype that were not previously attributed to LIF overexpression. First, they display B cell hyperplasia, polyclonal hypergammaglobulinemia and mesangial proliferative glomerulonephritis, defects similar to those described for transgenic mice overexpressing the functionally related cytokine, interleukin-6. Secondly, the LIF transgenic 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 CD4+CD8+ lymphocyte population. Furthermore, the thymic epithelium is profoundly disorganized, suggesting that disruption of stroma-lymphocyte interactions is responsible for many observed defects. Transplantation of transgenic bone marrow into wild type recipients transfers both the thymic and lymph node defects. However, transplantation of wild type marrow into transgenic recipients rescues the lymph node abnormality, but not the thymic defect, indicating the thymic epithelium is irreversibly altered. Our observations are consistent with a role for LIF in maintaining a functional thymic epithelium that will support proper T cell maturation.
Shen
M M
MM
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
Skoda
R C
RC
Cardiff
R D
RD
Campos-Torres
J
J
Leder
P
P
Ornitz
D M
DM
D000818:Animals; D001769:Blood; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D016516:CD4-CD8 Ratio; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology*; D006942:Hypergammaglobulinemia / Q000209:etiology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines