Triiodothyronine modulates differential homing of recent thymic emigrants to peripheral lymphoid organs.

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 (T(3)) could influence the homing of thymus-derived T cells. For that we used intrathymic injection of T(3) in combination with fluorescein isothiocyanate (FITC) to trace, 16 h later, FITC(+) cells, termed RTE, in peripheral lymphoid organs. We observed that T(3) 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. T(3) 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 T(3) 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.

Triiodothyronine modulates thymocyte migration.

Triiodothyronine (T(3)) exerts several effects on thymus physiology. In this sense, T(3) is known to stimulate thymic microenvironmental cells to enhance the production of extracellular matrix (ECM) moieties, which are relevant in thymocyte migration. Here, we further investigated the in vivo influence of T(3) on ECM production, as well as on ECM-related T-cell migration events. For this, BALB/c mice were subjected to two protocols of T(3) treatment: long-term (30 days) i.p. daily T(3) injections or short-term (16 h) after a single T(3) intrathymic injection. These two treatments did promote an enhancement in the expression of fibronectin and laminin, in both cortex and medullary regions of the thymic lobules. As revealed by the long-term treatment, the expression of ECM protein receptors, including VLA-4, VLA-5 and VLA-6, was also increased in thymocyte subsets issued from T(3)-treated mice. We further used thymic nurse cells (TNC) as an in vitro system to study the ECM-related migration of immature thymocytes in the context of thymic epithelial cells. Even a single intrathymic injection of T(3) resulted in an increase in the ex vivo exit of thymocytes from TNC lymphoepithelial complexes. Accordingly, when we evaluated thymocyte migration in transwell chambers pre-coated with ECM proteins, we found an increase in the numbers of migrating cells, when thymocytes were derived from T(3)-treated mice. Overall, our data show that in vivo intrathymic short-term i.p. long-term T(3) treatments are able to modulate thymocyte migration, probably via ECM-mediated interactions.

Leptin injection during lactation alters thyroid function in adult rats.

The aim of this study was to evaluate the effects of hyperleptinemia during the first ten days of life on thyroid function in adulthood. After birth, pups were separated into two groups: L8 - receiving daily injections of recombinant mouse leptin (8 microg/100 g body weight, sc) and control (C) - receiving the same volume of saline. Both groups were treated for the first 10 days of lactation. The animals were sacrificed at 150 days of age, and the blood was collected for leptin, TSH, total triiodothyronine (TT 3 ) and total thyroxin (TT 4 ) serum concentration determinations by radioimmunoassay. The thyroid gland was excised to determine thyroid iodine uptake. Leptin, TT 3 and TT 4 serum concentrations in L8 group were significantly (108 %, 47 % and 32 %; p < 0.05) higher than that of controls. There was no significant difference between the groups related to thyroid iodine uptake and TSH serum concentration. These data suggest that the first half of lactation period is important in determining thyroid function in adulthood, and that it can be programmed by serum leptin concentration.

Long-term effects of malnutrition during lactation on the thyroid function of offspring.

Some studies have shown that the mother's nutritional condition may influence offspring's endocrine function through metabolic imprinting. Recently, we showed that the kind of maternal malnutrition during lactation affects adult body weight of the offspring and it is related to milk composition. We studied lactating rats fed an 8 % protein-restricted diet (PR), a control 23 % protein diet (C), and an energy-restricted diet group (ER). After weaning, all animals received a normal diet until they were 180 days of age. At this time, the animals received a single i. p. injection of (131)I and were sacrificed 2 h after the injection. Total triiodothyronine (TT3) and total thyroxin (TT4) serum concentrations were measured by enzyme immunoassay. The PR group had significantly a higher thyroid (131)I uptake, TT3 serum concentration and in TT4 serum concentration, compared to the controls. The ER group had only significantly higher TT3 serum concentration. These results showed that thyroid function regulation in adulthood may depend on maternal nutritional condition during lactation. Probably, PR group had a high thyroid function, whereas the ER group only had an increase in the deiodination of T4. The hyperthyroidism in the PR group could explain the low body weight observed in those animals.