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Abnormal thymic microenvironment in insulin-like growth factor-II transgenic mice.
- Source :
-
Neuroimmunomodulation [Neuroimmunomodulation] 2005; Vol. 12 (2), pp. 100-12. - Publication Year :
- 2005
-
Abstract
- Objectives: Intrathymic T cell differentiation is driven by the thymic microenvironment, a tridimensional network of cells and extracellular matrix (ECM). Previous data showed that lymphoid and microenvironmental compartments are under the control of hormones and growth factors. We then attempted to define if insulin-like growth factor-II (IGF-II) was also involved in such a control.<br />Methods: We used IGF-II transgenic (Tg) mice and studied their thymic microenvironment by immunohistochemistry. Moreover, we evaluated thymocytes in terms of their ability to adhere to thymic epithelial cells and to migrate through epithelial cells and ECM.<br />Results: Transgenic IGF-II expression results in abnormalities of the thymic epithelium. Terminal differentiation of thymic epithelial cells (TEC) is modified, with the appearance of large clusters of cells immunoreactive to the monoclonal antibody KL1, which specifically recognizes highly differentiated TEC. Accordingly, treatment of cultured TEC with exogenous IGF-II induces the appearance of KL1+ cells and increases TEC proliferation. IGF-II Tg animals exhibit increased serum levels of the TEC-derived hormone thymulin. These effects were seen even when the IGF-II transgene was inserted in dwarf mice. Moreover, deposition of fibronectin and laminin is also enhanced in IGF-II Tg mouse thymus and in IGF-II-treated TEC cultures. Furthermore, ECM-mediated interactions between thymocytes and TEC are affected by exogenous IGF-II, as exemplified by the enhancement of thymocyte adhesion to TEC monolayers and thymocyte migration in thymic nurse cell complexes.<br />Conclusions: Our data indicate that IGF-II pleiotropically affects the thymic epithelium, both in vivo and in vitro, and that some of these changes may have consequences on thymocyte/TEC interactions.
- Subjects :
- Animals
Antibodies, Monoclonal
Cell Adhesion drug effects
Cell Adhesion physiology
Cell Differentiation drug effects
Cell Movement drug effects
Cell Movement physiology
Cell Proliferation drug effects
Cells, Cultured
Epithelial Cells cytology
Epithelial Cells drug effects
Extracellular Matrix drug effects
Fibronectins metabolism
Gene Expression Regulation drug effects
Gene Expression Regulation physiology
Immunohistochemistry
Insulin-Like Growth Factor II pharmacology
Laminin metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
T-Lymphocytes cytology
Thymic Factor, Circulating metabolism
Thymus Gland metabolism
Up-Regulation drug effects
Up-Regulation physiology
Cell Differentiation physiology
Epithelial Cells metabolism
Extracellular Matrix metabolism
Insulin-Like Growth Factor II genetics
T-Lymphocytes metabolism
Thymus Gland abnormalities
Thymus Gland cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1021-7401
- Volume :
- 12
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuroimmunomodulation
- Publication Type :
- Academic Journal
- Accession number :
- 15785112
- Full Text :
- https://doi.org/10.1159/000083582