Is there a role for growth hormone upon intrathymic T-cell migration?
Intrathymic T-cell differentiation is essentially driven by the thymic microenvironment, a tridimensional network formed by thymic epithelial cells and to a lesser extent, dendritic cells, macrophages, fibroblasts, and extracellular matrix components. Thymocyte migration throughout the thymus is partially dependent on extracellular-matrix (ECM)-mediated interactions. Herein we investigated the putative role of growth hormone (GH) upon events related to intrathymic T-cell migration. We demonstrated that GH upregulates the expression of ECM ligands and receptors in distinct preparations of cultured thymic epithelial cells TECs). We also showed that adhesion of thymocytes to thymic epithelial cells was significantly increased by GH treatment, an effect that could be consistently abrogated when TECs were treated to antifibronectin, anti-VLA5, antilaminin, or anti-VLA6 antibodies before addition of thymocytes to the cultures. We also studied thymic nurse cells (TNCs), lymphoepithelial complexes that can be isolated ex vivo from the thymus. In this system, we had previously demonstrated that ECM ligands and receptors control both inward and outward thymocyte traffic. We then showed that GH enhances thymocyte release from TNCs, as well as the reconstitution of these lymphoepithelial complexes. Lastly, we evaluated the in vivo influence of GH on thymocyte exit. This was done by means of intrathymic injection of GH plus fluorescein isothiocyanate (FITC), and further analysis of recent thymic emigrants (FITC+ cells) in peripheral lymphoid organs, as defined by CD4/CD8-based cytofluorometric phenotyping. The proportions of FITC+ T cells appeared augmented in lymph nodes in GH-treated mice, as compared to controls. Taken together, these data indicate that GH stimulates intrathymic T-cell traffic, an effect that is at least partially mediated by extracellular matrix-mediated interactions.
Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Avenue Brasil 4365-Manguinhos, 21045-000 Rio de Janeiro, RJ, Brazil. savino@gene.dbbm.fiocruz.br
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Savino
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Smaniotto
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De Mello-Coelho
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M
Dardenne
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D015213:Neuroimmunomodulation; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology*
D013006:Growth Hormone