Cyclical mobilization and gated importation of thymocyte progenitors in the adult mouse: evidence for a thymus-bone marrow feedback loop

Abstract

It has recently been observed, as in the fetal thymus, that the importation of hematogenous thymocyte progenitors by the adult thymus is a gated phenomenon, whereby saturating numbers of progenitors periodically enter the thymus and occupy a finite number of intrathymic niches. In addition, the mobilization of thymocyte progenitors from the bone marrow appears to be a cyclical process that coincides temporally with the periods of thymic receptivity (open gate). It is proposed that these events are coordinated by a thymus-bone marrow feedback loop in which a wave of developing triple negative (CD3- CD4- CD8-) thymocytes interacts with stromal cells in the stratified regions of the thymus cortex to sequentially induce the release of diffusible cytokines that regulate the production, mobilization, and recruitment of thymocyte progenitors. The likely components of this feedback loop are described here, as are the properties of the intrathymic vascular gates and niches for thymocyte progenitors. The cyclical production and release of thymocyte progenitors from the bone marrow is placed in the context of a general phenomenon of oscillatory feedback regulation involving all lymphohemopoietic cell lineages. Lastly, the question of whether the gated (as opposed to the continuous) entry of thymocyte progenitors is essential for normal thymocytopoiesis in adult life is discussed.