The Importation of Hematogenous Precursors by the Thymus Is a Gated Phenomenon in Normal Adult Mice

Abstract

Hematogenous precursors repopulate the thymus of normal adult mice, but it is not known whether this process is continuous or intermittent. Here, two approaches were used to demonstrate that the importation of prothymocytes in adult life is a gated phenomenon. In the first, age-dependent receptivity to thymic chimerism was studied in nonirradiated Ly 5 congenic mice by quantitative intrathymic and intravenous bone marrow (BM) adoptive transfer assays. In the second, the kinetics of importation of blood-borne prothymocytes was determined by timed separation of parabiotic mice. The results showed that >60% of 3–18-wk-old mice developed thymic chimerism after intrathymic injection of BM cells, and that the levels of chimerism (range, 5–90% donor-origin cells) varied cyclically (periodicity, 3 to 5 wk). In contrast, only 11–14% of intravenously injected recipients became chimeric, and chimerism occurred intermittently (receptive period ∼1 wk; refractory period ∼3 wk). In the intravenously injected mice, chimerism occurred simultaneously in both thymic lobes; gate opening occurred only after most intrathymic niches for prothymocytes had emptied; and the ensuing wave of thymocytopoiesis encompassed two periods of gating. These kinetics were confirmed in parabiotic mice, and in cohorts of mice in whom gating was synchronized by an initial intrathymic injection of BM cells. In addition, a protocol was developed by which sequential intravenous injections of BM cells over a 3 to 4 wk period routinely induces thymic chimerism in the apparent absence of stem cell chimerism. Hence, the results not only provide a new paradigm for the regulation of prothymocyte importation during adult life, but may also have applied implications for the selective induction of thymocytopoiesis in nonmyeloablated hosts.

Two Developmentally Distinct Populations of Dendritic Cells Inhabit the Adult Mouse Thymus: Demonstration by Differential Importation of Hematogenous Precursors Under Steady State Conditions

“…We approached this objective by using a combination of unmanipulated, parabiotic, and irradiated mice similar to that which we previously used to define the kinetics of prothymocyte importation and thymocytopoiesis in normal adult mice (25)(26)(27). The results provided clear evidence for the existence of two developmentally distinct populations of thymic DCs whose precursors are differentially imported from the blood.…”

“…For example, we have recently demonstrated that the importation of prothymocytes is a gated phenomenon in normal adult mice (25), that newly generated prothymocytes are exported from bone marrow (BM) intermittently rather than continuously (D. Foss and I. Goldschneider, manuscript in preparation), and that newly imported prothymocytes compete for a finite number of i.t. binding sites (putative microenvironmental niches) (26).…”

The role of apoptosis in the development and function of T lymphocytes

“…In adults, thymocyte development begins with the migration of multipotent precursors from the bone marrow into the thymus. These precursor cells periodically enter the thymus through postcapillary venules in the cortex region close to the corticomedullary junction [126,127]. After entering the thymus, the precursor cells differentiate into DN1 cells (CD44 + CD25 -).…”

A Role for CCR9 in T Lymphocyte Development and Migration

“…quires the periodic migration of progenitor cells from the bone marrow to the thymus (1,2). The ordered progression of thymocytes through distinct stages of development is also associated with the migration of cells into and between different thymic microenvironments (3).…”