[Human hematopoiesis: from CD34 cells to T lymphocytes]

Abstract

Hematopoietic stem cell (HSC) has two key-properties : the self-renewal and the multipotentiality which guarantee the homeostasis of the hematopoietic system all along the lifespan. Inside this system, T lymphocytes are particular for several reasons. First and foremost, their differentiation takes place in a different organ from the one where the immature progenitors are generated and expanded. This implies the migration of an immature progenitor from the fetal liver and later on from the bone marrow to the thymus. Secondly, T cell differentiation is characterized by thymic selection and generation of T lymphocytes with a diverse repertoire able to answer to all foreign antigens one can meet. These complicated mechanisms underlying the T cell differentiation, completely different from those characterizing the myeloid system, at least partially explain our limited knowledge on human T cell lymphopoiesis. Finally, T cell differentiation pathway shows the particularity of profound ontogenic changes with the huge production of lymphoid progenitors during the fetal and the first years of life which declines during the ageing period. Recently, the discovery of new hematopoietic cytokines, the discovery of genes involved in primary immunodeficiencies and the detailed description of the role of Notch receptors have strongly developed our knowledge on T cell lymphopoiesis. In this review, we will attempt to describe where we stand in the description of this fundamental process and to underline the unresolved questions. The knowledge of this process is crucial, since it will lead us to set up new protocols with the aim to speed up immunological reconstitution after HLA partially compatible HSC and to treat the lymphocytopenia of patients affected by HIV.