Intrathymic T Cell Migration Is a Multivectorial Process under a Complex Neuroendocrine Control

Abstract

The thymus is responsible for normal T cell development, a process that includes cell proliferation, death, migration, and T cell receptor gene rearrangements. Moreover, it depends on interactions between developing thymocytes and thymic microenvironmental cells. Along with differentiation, thymocytes migrate and such oriented movement is regulated by several molecular interactions, comprising extracellular matrix (ECM) elements and chemokines. We postulated that intrathymic T cell migration is a multivectorial process; each individual vector being represented by a given molecular interaction. In vivo and in vitro experiments revealed that migration of developing thymocytes, including the export of mature T cells, is upregulated by hormones, such as growth hormone and triiodothyronine, through the modulation of ECM-mediated interactions, associated or not with the chemokine CXCL12. Recent data revealed that molecular interactions typically found in the nervous system also affect intrathymic T cell migration. Semaphorin-3A, a soluble member of the semaphorin family, is involved in the control of human thymocyte migration, bearing a chemorepulsive role. Such an effect is partially due to its downregulatory effect upon the interactions mediated by fibronectin and laminin, as well as CXCL12. These data unravel a complex neuroendocrine control intrathymic T cell migration, involving both endocrine and paracrine molecular interactions.