Objectives: Thyroid hormones exert immunomodulatory activities and the thymus is one of their target organs. We previously showed that triiodothyronine (T₃) 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 T₃ 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 T₃. Interestingly, TEC-thymocyte adhesion is also upregulated when thymocytes from T₃-treated mice adhere to untreated TEC cultures. Such an enhancing effect of T₃ upon TEC-thymocyte interactions is likely due to the increase in the expression of ECM ligands and receptors, since it is prevented when T₃-treated TEC cultures are incubated with anti-ECM antibodies prior to the adhesion assay. We then tested whether T₃ 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 T₃ 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 T₃ receptor in all thymic microenvironmental cell preparations. Conclusion: Our data show that T₃ upregulates ECM-mediated heterocellular interactions of thymocytes with distinct thymic microenvironmental cells, in both humans and mice.

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.

SummaryMultidrug-resistant tuberculosis (MDR-TB) is known as having a poor prognosis with a weak response to therapy and very high death rates. The aim of this work was to assess the immune response to the RD1-encoded antigen ESAT-6 of Mycobacterium tuberculosis in MDR-TB patients and compare to non-resistant (NR) TB patients and healthy controls (HC). Evaluation of interferon (IFN)-g g g g production showed that, although 55% of the MDR patients were responsive to ESAT-6, they produced lower IFN-g g g g levels (553 ± ± ± ± 11 pg/ml) when compared to NR-TB (1179 ± ± ± ± 163 pg/ml; P < < < < 0·05) but not to controls (412 ± ± ± ± 65·7 pg/ml). Differences in the response to ESAT-6 and to its overlapping peptides mixture were also significant between MDR versus treated pulmonary NR-TB. Furthermore, a very low rate of response to PPD (23·5%) and to Ag85B (33·3%) was noted in MDR-TB patients as compared to the other groups. To determine the inflammatory response in patients' groups, detection of tumour necrosis factor (TNF)-a a a a was assessed in their sera before and during chemotherapy. Mean TNF-a a a a levels in MDR-TB (43·8 ± ± ± ± 9 pg/ml) paralleled those found in treated pulmonary, and it was significantly different ( P < < < < 0·05) from the values found in untreated NR and HC. Interestingly, secretion of IFN-g g g g and TNF-a a a a were predominant in MDR patients who presented with bilateral pulmonary lesions and lung cavitation. The present data indicate that the overall immune response to mycobacterial antigens is decreased in resistant TB and the major role inflammatory cytokines may play in perpetuating pulmonary tissue damage.

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This study confirmed the feasibility of obtaining ex vivo macrophages from leprosy lesions and keeping them in long-term culture. This procedure may open new pathways to studying the interaction between M. leprae and human macrophages, which might, in turn, lead to the development of therapeutic tools capable of overcoming the specific anergy found in patients with MB leprosy.