       Document 0134
 DOCN  M9460134
 TI    Expression of LIF in transgenic mice results in altered thymic
       epithelium and apparent interconversion of thymic and lymph node
       morphologies.
 DT    9404
 AU    Shen MM; Skoda RC; Cardiff RD; Campos-Torres J; Leder P; Ornitz DM;
       Howard Hughes Medical Institute, Harvard Medical School, Boston,; MA
       02115.
 SO    EMBO J. 1994 Mar 15;13(6):1375-85. Unique Identifier : AIDSLINE
       MED/94185644
 AB    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.
 DE    Animal  Blood  Bone Marrow/CYTOLOGY  Bone Marrow Transplantation
       CD4-CD8 Ratio  Epithelium/CYTOLOGY/METABOLISM  Growth
       Inhibitors/GENETICS/*PHYSIOLOGY  Hypergammaglobulinemia/ETIOLOGY  Lymph
       Nodes/CYTOLOGY/*METABOLISM  Lymphokines/GENETICS/*PHYSIOLOGY  Mice
       Mice, Transgenic  Phenotype  Support, Non-U.S. Gov't
       T-Lymphocytes/CYTOLOGY/IMMUNOLOGY  Thymus Gland/CYTOLOGY/*METABOLISM
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

