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The importation of hematogenous precursors by the thymus is a gated phenomenon in normal adult mice.

Foss DL, Donskoy E, Goldschneider I - J. Exp. Med. (2001)

Bottom Line: In contrast, only 11-14% of intravenously injected recipients became chimeric, and chimerism occurred intermittently (receptive period approximately 1 wk; refractory period approximately 3 wk).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, School of Medicine, The University of Connecticut Health Center, Farmington, Connecticut 06030, USA.

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 approximately 1 wk; refractory period approximately 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.

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Intrathymic gating is synchronized by initial intrathymic (I.T.) injection of BM cells. A cohort of 5-wk-old (± 3 d) Ly 5.1 mice was injected intrathymically with a saturating dose of Ly 5.1 BM cells, and at weekly intervals thereafter a separate group of 9–12 of these mice was reinjected with saturating doses of Ly 5.2 BM cells (A and B) intrathymically or (C and D) intravenously. The percentage of Ly 5.2 thymocytes present 28 d later was determined by FCM analysis. The frequencies (A and C) and mean levels (B and D) of thymic chimerism within each group were plotted as a function of age. Percentage of chimeric mice (≥5% donor-origin cells) after intrathymic injection = 62. Percentage of chimeric mice after intravenous (I.V.) injection = 13.8.
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Figure 6: Intrathymic gating is synchronized by initial intrathymic (I.T.) injection of BM cells. A cohort of 5-wk-old (± 3 d) Ly 5.1 mice was injected intrathymically with a saturating dose of Ly 5.1 BM cells, and at weekly intervals thereafter a separate group of 9–12 of these mice was reinjected with saturating doses of Ly 5.2 BM cells (A and B) intrathymically or (C and D) intravenously. The percentage of Ly 5.2 thymocytes present 28 d later was determined by FCM analysis. The frequencies (A and C) and mean levels (B and D) of thymic chimerism within each group were plotted as a function of age. Percentage of chimeric mice (≥5% donor-origin cells) after intrathymic injection = 62. Percentage of chimeric mice after intravenous (I.V.) injection = 13.8.

Mentions: We therefore attempted to synchronize intrathymic gating in a cohort of 5-wk-old (± 3 d) Ly 5.1 mice by first filling all available niches for prothymocytes by intrathymic injection of host allotype BM cells. Subsequent intrathymic or intravenous injections of Ly 5.2 BM cells documented the resulting synchronization of chimerism with time. As shown in Fig. 6A and Fig. B, the frequencies and mean levels of thymic chimerism after intrathymic injection occurred in two clearly defined cycles. Each peak was preceded by an ∼2-wk period of increasing availability of putative niches for prothymocytes, followed by a 2-wk period of decreasing availability of niches (presumably due to occupation by recently imported host-origin precursors).


The importation of hematogenous precursors by the thymus is a gated phenomenon in normal adult mice.

Foss DL, Donskoy E, Goldschneider I - J. Exp. Med. (2001)

Intrathymic gating is synchronized by initial intrathymic (I.T.) injection of BM cells. A cohort of 5-wk-old (± 3 d) Ly 5.1 mice was injected intrathymically with a saturating dose of Ly 5.1 BM cells, and at weekly intervals thereafter a separate group of 9–12 of these mice was reinjected with saturating doses of Ly 5.2 BM cells (A and B) intrathymically or (C and D) intravenously. The percentage of Ly 5.2 thymocytes present 28 d later was determined by FCM analysis. The frequencies (A and C) and mean levels (B and D) of thymic chimerism within each group were plotted as a function of age. Percentage of chimeric mice (≥5% donor-origin cells) after intrathymic injection = 62. Percentage of chimeric mice after intravenous (I.V.) injection = 13.8.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2195915&req=5

Figure 6: Intrathymic gating is synchronized by initial intrathymic (I.T.) injection of BM cells. A cohort of 5-wk-old (± 3 d) Ly 5.1 mice was injected intrathymically with a saturating dose of Ly 5.1 BM cells, and at weekly intervals thereafter a separate group of 9–12 of these mice was reinjected with saturating doses of Ly 5.2 BM cells (A and B) intrathymically or (C and D) intravenously. The percentage of Ly 5.2 thymocytes present 28 d later was determined by FCM analysis. The frequencies (A and C) and mean levels (B and D) of thymic chimerism within each group were plotted as a function of age. Percentage of chimeric mice (≥5% donor-origin cells) after intrathymic injection = 62. Percentage of chimeric mice after intravenous (I.V.) injection = 13.8.
Mentions: We therefore attempted to synchronize intrathymic gating in a cohort of 5-wk-old (± 3 d) Ly 5.1 mice by first filling all available niches for prothymocytes by intrathymic injection of host allotype BM cells. Subsequent intrathymic or intravenous injections of Ly 5.2 BM cells documented the resulting synchronization of chimerism with time. As shown in Fig. 6A and Fig. B, the frequencies and mean levels of thymic chimerism after intrathymic injection occurred in two clearly defined cycles. Each peak was preceded by an ∼2-wk period of increasing availability of putative niches for prothymocytes, followed by a 2-wk period of decreasing availability of niches (presumably due to occupation by recently imported host-origin precursors).

Bottom Line: In contrast, only 11-14% of intravenously injected recipients became chimeric, and chimerism occurred intermittently (receptive period approximately 1 wk; refractory period approximately 3 wk).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, School of Medicine, The University of Connecticut Health Center, Farmington, Connecticut 06030, USA.

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 approximately 1 wk; refractory period approximately 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.

Show MeSH
Related in: MedlinePlus