Trafficking on serpentines: molecular insight on how maturating T cells find their winding paths in the thymus

Maintenance of the peripheral T-cell pool throughout the life requires uninterrupted generation of T cells. The majority of peripheral T cells are generated in the thymus. However, the thymus does not contain hematopoietic progenitors with unlimited self-renewing potential, and continuous production of T cells requires importation of such progenitors from the bone marrow into the thymus. Thymus-homing progenitors enter the thymus and subsequently migrate throughout distinct intrathymic microenvironments while differentiating into mature T cells. At each step of this scheduled journey, developing thymocytes interact intimately with the local stroma, which allow them to proceed to the next stage of their differentiation and maturation program. Undoubtedly, thymocyte/stroma interactions are instrumental for both thymocytes and stroma, because only their ongoing interplay generates and maintains a fully operational thymus, able to guarantee unimpaired T-cell supply. Therefore, proper T-cell generation intrinsically involves polarized cell migration during both adult life and embryogenesis when the thymus primordium develops into a functional thymus. The molecular mechanisms controlling cell migration during thymus development and postnatal T-cell differentiation are beginning to be defined. This review focuses on recent data regarding the role of cell migration in both colonization of the fetal thymus and T-cell development during postnatal life in mice.