Zoned Out: Functional Mapping of Stromal Signaling Microenvironments in the Thymus

All hematopoietic cells, including T lymphocytes, originate from stem cells that reside in the bone marrow. Most hematopoietic lineages also mature in the bone marrow, but in this respect, T lymphocytes differ. Under normal circumstances, most T lymphocytes are produced in the thymus from marrow-derived progenitors that circulate in the blood. Cells that home to the thymus from the marrow possess the potential to generate multiple T and non-T lineages. However, there is little evidence to suggest that, once inside the thymus, they give rise to anything other than T cells. Thus, signals unique to the thymic microenvironment compel multipotent progenitors to commit to the T lineage, at the expense of other potential lineages. Summarizing what is known about the signals the thymus delivers to uncommitted progenitors, or to immature T-committed progenitors, to produce functional T cells is the focus of this review.