Triiodothyronine Modulates Differential Homing of Recent Thymic Emigrants to Peripheral Lymphoid Organs

Abstract

The functioning of the immune system partially relies on T‐cell exportation from the thymus, the major site of T‐cell differentiation. Although the molecular mechanisms governing this process begin to be elucidated, it is not clear if thyroid hormones can alter the homing of recent thymic emigrants (RTE) to peripheral lymphoid organs. Herein, we investigated whether triiodothyronine (T3) could influence the homing of thymus‐derived T cells. For that we used intrathymic injection of T3 in combination with fluorescein isothiocyanate (FITC) to trace, 16 h later, FITC+ cells, termed RTE, in peripheral lymphoid organs. We observed that T3 stimulated thymocyte export, increasing the frequency of CD4+ RTE and CD8+ RTE in the subcutaneous and mesenteric lymph nodes. By contrast, the relative numbers of CD4+ RTE in the spleen were decreased. T3 also changed the differential distribution pattern of CD4+ RTE, and to a lesser extent CD8+ RTE in the peripheral lymphoid organs. Moreover, the expression of extracellular matrix (ECM) components, such as laminin and fibronectin, which are known to be involved in T‐cell migration, increased in the lymph nodes but not in the spleen following intrathymic T3 treatment. In conclusion, our data correspond to the first demonstration that in vivo treatment with thyroid hormone stimulates thymic T‐cell homing and T‐cell distribution in peripheral lymphoid organs.

High levels of circulating triiodothyronine induce plasma cell differentiation

“…We also noted that the increase in the spleen weight and cellularity observed in T 3 -treated mice was, at least in part, due to an increase in the number of splenic B lymphocytes in these animals; however, other cell types may also be affected. In this regard, we previously showed that intrathymic injection of T 3 stimulates the output of T-cells to peripheral lymphoid organs in mice (Ribeiro-Carvalho et al 2007). In addition, Klecha et al (2005) demonstrated an increase in the mitogen-induced T-cell proliferation in mice previously treated with T 4 .…”

“…These processes are regulated, at least in part, by extracellular matrix and chemokine molecules (Mebius & Kraal 2005, Lokmic et al 2008. In this regard, we have previously shown that mice treated with T 3 exhibited modulation of extracellular matrix components in the spleen, increasing the expression of laminin and fibronectin glycoproteins (Ribeiro-Carvalho et al 2007). However, additional studies are still necessary to verify whether TH excess regulates B-cell homing by modulating the levels of extracellular matrix molecules and chemokine expression and responsiveness.…”

Growth hormone enhances thymic function in HIV-1–infected adults

“…Thus, murine studies have demonstrated that GH therapy promotes the accumulation of RTEs in peripheral lymphoid tissues by increasing RTE expression of adhesion molecules (49,50). IL-7 and thyroid hormone also have been found to promote accumulation of TREC-bearing naive T cells and RTEs in lymphoid tissues (51,52).…”

Impairment of Regulatory Capacity of CD4+CD25+ Regulatory T Cells Mediated by Dendritic Cell Polarization and Hyperthyroidism in Graves’ Disease

“…Notably, evidence indicates functional cross talk between immune and endocrine systems in the modulation of innate and adaptive immunity, such as the immunosuppressive effects of thyroxine on T and B cells in C57BL/6 mice (50), suppression of peripheral blood NK cell activity by excess thyroid hormone (51), modulation of differential homing of CD4 + T cells and CD8 + T cells to peripheral lymphoid organs (52), and control of maturation and function of DCs by triiodothyronine (53,54). Because the polarization and effect of uGD-derived DCs are found in uGD patients with elevated THs, it is necessary to determine the effect of elevated THs on DCs and Treg cells.…”