Factors regulating stem cell recruitment to the fetal thymus

Colonization of the thymic rudiment during development is initiated before vascularization so that hemopoietic precursors must leave the pharyngeal ve ssels and migrate through the perithymic mesenchyme to reach the thymus, su ggesting that they may be responding to a gradient of chemoattractant facto rs. We report that diffusible chemoattractants are produced by MHC class II + epithelial cells of the fetal thymus, and that the response of precursors to these factors is mediated via a G protein coupled receptor, consistent with factors being members of the chemokine family. Indeed, a number of che mokine receptors are expressed by thymic precursors, and several chemokines are also expressed by thymic epithelial cells, However, these chemokines a re also expressed in a tissue that is unable to attract precursors, althoug h the thymus expressed chemokine, TECK, is expressed at higher levels in th ymic epithelial cells and we show that it has chemotactic activity for isol ated thymic precursors. Neutralizing Ab to TECK, however, did not prevent t hymus recolonization by T cell precursors, suggesting that other novel chem okines might be involved in this process. In addition, we provide evidence for the involvement of matrix metalloproteinases in chemoattractant-mediate d T cell precursor recruitment to the thymus during embryogenesis.