Growth hormone stimulates the selective trafficking of thymic CD4+CD8- emigrants to peripheral lymphoid organs.

Growth hormone (GH) has been shown to stimulate T cell development. However, its mechanisms of action on the peripheral T cell pool remain unknown. To address this question, intrathymic injection of GH in combination with fluorescein isothiocyanate (FITC) was used to assess the effects of GH on T cell trafficking from the thymus to the periphery. GH promoted a significant increase in the percentage and differential distribution of thymic CD4+CD8-FITC+ cells in secondary lymphoid organs. A significantly higher percentage of CD4+CD8-FITC+ cells was observed in the lymph nodes, while a relative decrease of these cells was found in the spleen. Moreover, we verified that GH treatment resulted in increased numbers of CD62L+CD4+CD8-FITC+ T cells in the lymph nodes, while the same treatment resulted in a decline in the percentage of VLA-6+CD4+CD8-FITC+ T cells in the spleen. Together, these findings suggest that GH is a potent immunoregulatory molecule which selectively stimulates the preferential homing of CD4+CD8- thymic emigrants to the subcutaneous lymph nodes possibly via the differential expression of CD62L and VLA-6.

Triiodothyronine modulates extracellular matrix-mediated interactions between thymocytes and thymic microenvironmental cells.

OBJECTIVES: Thyroid hormones exert immunomodulatory activities and the thymus is one of their target organs. We previously showed that triiodothyronine (T(3)) modulates thymic hormone production and extracellular matrix (ECM) expression by mouse thymic epithelial cells (TEC). This concept is enlarged herein by studying the effects of T(3) in human TEC preparations including primary cultures derived from thymic nurse cell complexes, as well as human and murine TEC lines. METHODS AND RESULTS: We observed that in all cases, ECM ligands and receptors (such as fibronectin, laminin, VLA-5 and VLA-6) are enhanced in vitro, as ascertained by immunocytochemistry, ELISA and cytofluorometry. Moreover, thymocyte adhesion to these TEC preparations is augmented by T(3). Interestingly, TEC-thymocyte adhesion is also upregulated when thymocytes from T(3)-treated mice adhere to untreated TEC cultures. Such an enhancing effect of T(3) upon TEC-thymocyte interactions is likely due to the increase in the expression of ECM ligands and receptors, since it is prevented when T(3)-treated TEC cultures are incubated with anti-ECM antibodies prior to the adhesion assay. We then tested whether T(3) could modulate interactions between thymocytes and nonepithelial microenvironmental cells, exemplified herein by the phagocytic cells of the mouse thymic reticulum. In fact, in vitro treatment of these cells with T(3) increases ECM ligands and receptors and augments their ability to adhere to thymocytes. Lastly, using immunochemistry-based assays, we showed the presence of the nuclear T(3) receptor in all thymic microenvironmental cell preparations. CONCLUSION: Our data show that T(3) upregulates ECM-mediated heterocellular interactions of thymocytes with distinct thymic microenvironmental cells, in both humans and mice.