Portal de Periódicos da CAPES

Mechanisms of thymus homing

1993; Elsevier BV; Volume: 81; Issue: 1 Linguagem: Inglês

10.1182/blood.v81.1.1.1

1528-0020

Dominique Dunon, BA Imhof,

Proteoglycans and glycosaminoglycans research

HYMUS COLONIZATION during embryogenesis startsT with the accumulation of basophilic cells in the jugular vein, in capillaries, and in the mesenchyme surrounding the thymus.In birds the extrinsic origin of these basophilic cells, which are considered to be hematopoietic precursors, was established by the construction of quail-chick chimeras.lS2Using this technique, Jotereau and Le Douarin3 and Coltey et a14 showed that the thymus of birds is colonized mainly in three waves during embryogenesis and the first few days after hatching.In mice, the thymus is colonized by hematopoietic precursors at days 10 and 13 of embryogenesis.'A similar process, albeit at much lower level, may occur throughout life?The major cellular events of thymus homing are illustrated in Fig 1.In birds, T-cell precursors first originate from para-aortic hematopoietic foci at the level of the ducts of Cuvier in 3- day-old quail embryos.','During the second and the third waves of thymus colonization, most T-cell precursors come from the bone marrow (BM).In mammals, the yolk sac contain precursors to T lymphocytes at a time of development when no lymphoid precursors could be found in the embryo proper' (and Palacios R, Imhof BA: submitted).In older embryos, intra-embryonic T-cell precursors are found in the 1 i ~e r .I ~' ~ After birth they are mainly produced in the BM.'49'5The homing of these precursors to the thymus has been extensively studied.Hematopoietic cells are transported via blood circulation from their site ofemergence to the thymus.16Early progenitors enter the nonvascularized thymic rudiment by the capsule, but pro-T cells could also enter the organ at the cortico-medullary j ~n c t i o n .' ~ After extravasation the Tcell precursors find themselves in a perivascular space rich in mesenchymal cells embedded in extracellular matrix.Finally, after invasive migration through the epithelial basal membrane, T-cell precursors interact with the thymic epithelium and other cells that constitute this complex microenvironment and consequently undergo differentiation along the T-cell pathway.The entire process of thymus colonization seems to occur rapidly, because fluorescein-labeled BM cells can be found in the thymus within 3 hours after intravenous (IV) injection.'' In this review, we summarize current knowledge on the molecules involved in thymus colonization identified so far and propose a model for the molecular mechanisms participating in this process (Fig 1).