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


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.


CONCLUSIONS
Our data show that T(3) upregulates ECM-mediated heterocellular interactions of thymocytes with distinct thymic microenvironmental cells, in both humans and mice.
Ribeiro-Carvalho
Marilza-Moura
MM
Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Farias-de-Oliveira
Désio Aurélio
DA
Villa-Verde
Déa Maria Serra
DM
Savino
Wilson
W
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D002675:Child, Preschool; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008807:Mice, Inbred BALB C; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D016326:Extracellular Matrix Proteins; D016201:Receptors, Lymphocyte Homing; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine