T cell homeostasis: Thymus regeneration and peripheral T cell restoration in mice with a reduced fraction of competent precursors

We developed a novel experimental strategy to study T cell regeneration aft er bone marrow transplantation. We assessed the fraction of competent precu rsors required to repopulate the thymus and quantified the relationship bet ween the size of the different T cell compartments during T cell maturation in the thymus. The contribution of the thymus to the establishment and mai ntenance of the peripheral T cell pools was also quantified. We found that the degree of thymus restoration is determined by the availability of compe tent precursors and that the number of double-positive thymus cells is not under homeostatic control. In contrast, the sizes of the peripheral CD4 and CD8 T cell pools are largely independent of the number of precursors and o f the number of thymus cells. Peripheral "homeostatic" proliferation and in creased export and/or survival of recent thymus emigrants compensate for re duced T cell production in the thymus. In spite of these reparatory process es, mice with a reduced number of mature T cells in the thymus have an incr eased probability of peripheral T cell deficiency, mainly in the naive comp artment.