Early steps of a thymic tumor in SV40 transgenic mice: hyperplasia of medullary epithelial cells and increased mature thymocyte numbers disturb thymic export.
Bone marrow progenitors migrate to the thymus, where they proliferate and differentiate into immunologically competent T cells. In this report we show that mice transgenic for SV40 T and t antigens under the control of the L-pyruvate kinase promoter develop, in a first step, thymic hyperplasia of both thymocytes and epithelial cells. Morphological studies (histology, immunohistolabeling and electron microscopy) revealed modifications of the thymic microenvironment and gradual expansion of medullary epithelial cells in 1 month-old mice, taking over the cortical region. Then, a thymic carcinoma develops. Two-color labeling of frozen sections identified the transgene in medullary epithelial cells. Flow cytometry analysis demonstrated a marked increase in mature CD4+ and CD8+ thymocytes in adult mice (39 +/- 10 x 10(6) in transgenic mice and 12 +/- 5 x 10(6) in age-matched controls). Furthermore, thymocyte export was disturbed.
Nabarra
Bernadette
B
INSERM U.345, Institut Necker, 75730, Paris Cedex 15, France.
Martinon
Catherine
C
Godard
Cécile
C
Vasseur
Florence
F
de Ribains
Geoffroy
G
Miquerol
Lucile
L
Kahn
Axel
A
Ezine
Sophie
S
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D013953:Thymus Neoplasms / Q000503:physiopathology*
D000952:Antigens, Polyomavirus Transforming; D011770:Pyruvate Kinase