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Ontogeny of the immune system: gamma/delta and alpha/beta T cells migrate from thymus to the periphery in alternating waves.

Dunon D, Courtois D, Vainio O, Six A, Chen CH, Cooper MD, Dangy JP, Imhof BA - J. Exp. Med. (1997)

Bottom Line: Each progenitor wave gave rise to gamma/delta T cells 3 d earlier than alpha/beta T cells.Although the flow of T cell migration from the thymus was uninterrupted, distinct colonization and differentiation kinetics defined three successive waves of gamma/delta and alpha/beta T cells that depart sequentially the thymus en route to the periphery.Each wave of precursors rearranged all three TCR Vgamma gene families, but displayed a variable repertoire.

View Article: PubMed Central - PubMed

Affiliation: Centre National de la Recherche Scientifique Unitè de Recherche Associée 1135, Université Pierre et Marie Curie, 75005 Paris, France. dunon@ccr.jussieu.fr

ABSTRACT
The embryonic thymus is colonized by the influx of hemopoietic progenitors in waves. To characterize the T cell progeny of the initial colonization waves, we used intravenous adoptive transfer of bone marrow progenitors into congenic embryos. The experiments were performed in birds because intravenous cell infusions can be performed more efficiently in avian than in mammalian embryos. Progenitor cells, which entered the vascularized thymus via interlobular venules in the capsular region and capillaries located at the corticomedullary junction, homed to the outer cortex to begin thymocyte differentiation. The kinetics of differentiation and emigration of the T cell progeny were analyzed for the first three waves of progenitors. Each progenitor wave gave rise to gamma/delta T cells 3 d earlier than alpha/beta T cells. Although the flow of T cell migration from the thymus was uninterrupted, distinct colonization and differentiation kinetics defined three successive waves of gamma/delta and alpha/beta T cells that depart sequentially the thymus en route to the periphery. Each wave of precursors rearranged all three TCR Vgamma gene families, but displayed a variable repertoire. The data indicate a complex pattern of repertoire diversification by the progeny of founder thymocyte progenitors.

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Migration pathways of thymocyte progenitors. Thymus sections from E13 H.B19ov− embryos injected with donor E13 H.B19ov+ bone  marrow cells were examined by differential immunofluorescence staining at E16, E19, E20, and E23. Donor ov+ progenitors are labeled with fluorescein;  TCR-γ/δ and TCR-α/β–positive cells are labeled with Texas red. Original magnifications: (A) 270, (B) 170. Scale bars correspond to 100 μm. (C) Diagrammatic representation of chicken T cell progenitor migration pathways in the thymus. At E16, T cell progenitors were located either in capillaries at  the cortico-medullary junction (a) or close to the thymic capsule (b). Donor cells originally located at the corticomedullary junction or at the capsule were  found later (E19) in the cortex, and by E20 had reached the outer cortex. By E23 (2 d after hatching), some donor cells were found in the medulla where  they expressed TCR-α/β (Vβ1) or TCR-γ/δ (d). The first TCR-γ+ donor cells were found on E19-20. c, cortex; m, medulla.
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Figure 1: Migration pathways of thymocyte progenitors. Thymus sections from E13 H.B19ov− embryos injected with donor E13 H.B19ov+ bone marrow cells were examined by differential immunofluorescence staining at E16, E19, E20, and E23. Donor ov+ progenitors are labeled with fluorescein; TCR-γ/δ and TCR-α/β–positive cells are labeled with Texas red. Original magnifications: (A) 270, (B) 170. Scale bars correspond to 100 μm. (C) Diagrammatic representation of chicken T cell progenitor migration pathways in the thymus. At E16, T cell progenitors were located either in capillaries at the cortico-medullary junction (a) or close to the thymic capsule (b). Donor cells originally located at the corticomedullary junction or at the capsule were found later (E19) in the cortex, and by E20 had reached the outer cortex. By E23 (2 d after hatching), some donor cells were found in the medulla where they expressed TCR-α/β (Vβ1) or TCR-γ/δ (d). The first TCR-γ+ donor cells were found on E19-20. c, cortex; m, medulla.

Mentions: The initial wave of progenitor colonization and thymocyte differentiation can be examined in situ in unmanipulated animals. However, analysis of members of the succeeding waves requires a discriminating strategy. Embryonic hemopoietic precursors express the ov antigen in H.B19ov+ birds, and the antigen is maintained on T lineage cells and a subset of B cells. This expression pattern allowed us to examine successive waves of the ov+ progenitor populations in the embryonic thymus and the fate of their T cell progeny in ov− congenic recipients. To examine the second wave of thymus colonization by progenitor cells, E13 bone marrow cells of the ov+ strain were injected into E13 chicken embryos of the congenic H.B19ov− strain, and the thymocyte progenitor influx, migration, and differentiation patterns were examined in thymus sections by immunohistochemistry. By E16, donor cells of bone marrow origin accumulated in the thymic blood vessels, both in interlobular venules and in capillaries located at the corticomedullary junction (Fig. 1); relatively few donor cells were found in the parenchyma of the thymus at this time. E19 ov+ cell invasion and accumulation within the thymic cortex was evident, but by E20 the donor cells had relocated to occupy the outermost cortex of the thymic lobules. This ontogenetic pattern suggests that thymocyte progenitors entering the embryonic thymus either via the corticomedullary junction or the capsular subsequently make their way to the outer cortex of the thymus (Fig.1 C). The donor cells were later found throughout the cortex and by day 23, mature ov+ donor T cells had begun to accumulate in the medulla. This complex intrathymic pattern of migration appears specific to bone marrow– derived thymocyte progenitors, since mature thymocytes and T cells failed to home to the thymus in other adoptive transfer experiments (not shown).


Ontogeny of the immune system: gamma/delta and alpha/beta T cells migrate from thymus to the periphery in alternating waves.

Dunon D, Courtois D, Vainio O, Six A, Chen CH, Cooper MD, Dangy JP, Imhof BA - J. Exp. Med. (1997)

Migration pathways of thymocyte progenitors. Thymus sections from E13 H.B19ov− embryos injected with donor E13 H.B19ov+ bone  marrow cells were examined by differential immunofluorescence staining at E16, E19, E20, and E23. Donor ov+ progenitors are labeled with fluorescein;  TCR-γ/δ and TCR-α/β–positive cells are labeled with Texas red. Original magnifications: (A) 270, (B) 170. Scale bars correspond to 100 μm. (C) Diagrammatic representation of chicken T cell progenitor migration pathways in the thymus. At E16, T cell progenitors were located either in capillaries at  the cortico-medullary junction (a) or close to the thymic capsule (b). Donor cells originally located at the corticomedullary junction or at the capsule were  found later (E19) in the cortex, and by E20 had reached the outer cortex. By E23 (2 d after hatching), some donor cells were found in the medulla where  they expressed TCR-α/β (Vβ1) or TCR-γ/δ (d). The first TCR-γ+ donor cells were found on E19-20. c, cortex; m, medulla.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2199063&req=5

Figure 1: Migration pathways of thymocyte progenitors. Thymus sections from E13 H.B19ov− embryos injected with donor E13 H.B19ov+ bone marrow cells were examined by differential immunofluorescence staining at E16, E19, E20, and E23. Donor ov+ progenitors are labeled with fluorescein; TCR-γ/δ and TCR-α/β–positive cells are labeled with Texas red. Original magnifications: (A) 270, (B) 170. Scale bars correspond to 100 μm. (C) Diagrammatic representation of chicken T cell progenitor migration pathways in the thymus. At E16, T cell progenitors were located either in capillaries at the cortico-medullary junction (a) or close to the thymic capsule (b). Donor cells originally located at the corticomedullary junction or at the capsule were found later (E19) in the cortex, and by E20 had reached the outer cortex. By E23 (2 d after hatching), some donor cells were found in the medulla where they expressed TCR-α/β (Vβ1) or TCR-γ/δ (d). The first TCR-γ+ donor cells were found on E19-20. c, cortex; m, medulla.
Mentions: The initial wave of progenitor colonization and thymocyte differentiation can be examined in situ in unmanipulated animals. However, analysis of members of the succeeding waves requires a discriminating strategy. Embryonic hemopoietic precursors express the ov antigen in H.B19ov+ birds, and the antigen is maintained on T lineage cells and a subset of B cells. This expression pattern allowed us to examine successive waves of the ov+ progenitor populations in the embryonic thymus and the fate of their T cell progeny in ov− congenic recipients. To examine the second wave of thymus colonization by progenitor cells, E13 bone marrow cells of the ov+ strain were injected into E13 chicken embryos of the congenic H.B19ov− strain, and the thymocyte progenitor influx, migration, and differentiation patterns were examined in thymus sections by immunohistochemistry. By E16, donor cells of bone marrow origin accumulated in the thymic blood vessels, both in interlobular venules and in capillaries located at the corticomedullary junction (Fig. 1); relatively few donor cells were found in the parenchyma of the thymus at this time. E19 ov+ cell invasion and accumulation within the thymic cortex was evident, but by E20 the donor cells had relocated to occupy the outermost cortex of the thymic lobules. This ontogenetic pattern suggests that thymocyte progenitors entering the embryonic thymus either via the corticomedullary junction or the capsular subsequently make their way to the outer cortex of the thymus (Fig.1 C). The donor cells were later found throughout the cortex and by day 23, mature ov+ donor T cells had begun to accumulate in the medulla. This complex intrathymic pattern of migration appears specific to bone marrow– derived thymocyte progenitors, since mature thymocytes and T cells failed to home to the thymus in other adoptive transfer experiments (not shown).

Bottom Line: Each progenitor wave gave rise to gamma/delta T cells 3 d earlier than alpha/beta T cells.Although the flow of T cell migration from the thymus was uninterrupted, distinct colonization and differentiation kinetics defined three successive waves of gamma/delta and alpha/beta T cells that depart sequentially the thymus en route to the periphery.Each wave of precursors rearranged all three TCR Vgamma gene families, but displayed a variable repertoire.

View Article: PubMed Central - PubMed

Affiliation: Centre National de la Recherche Scientifique Unitè de Recherche Associée 1135, Université Pierre et Marie Curie, 75005 Paris, France. dunon@ccr.jussieu.fr

ABSTRACT
The embryonic thymus is colonized by the influx of hemopoietic progenitors in waves. To characterize the T cell progeny of the initial colonization waves, we used intravenous adoptive transfer of bone marrow progenitors into congenic embryos. The experiments were performed in birds because intravenous cell infusions can be performed more efficiently in avian than in mammalian embryos. Progenitor cells, which entered the vascularized thymus via interlobular venules in the capsular region and capillaries located at the corticomedullary junction, homed to the outer cortex to begin thymocyte differentiation. The kinetics of differentiation and emigration of the T cell progeny were analyzed for the first three waves of progenitors. Each progenitor wave gave rise to gamma/delta T cells 3 d earlier than alpha/beta T cells. Although the flow of T cell migration from the thymus was uninterrupted, distinct colonization and differentiation kinetics defined three successive waves of gamma/delta and alpha/beta T cells that depart sequentially the thymus en route to the periphery. Each wave of precursors rearranged all three TCR Vgamma gene families, but displayed a variable repertoire. The data indicate a complex pattern of repertoire diversification by the progeny of founder thymocyte progenitors.

Show MeSH
Related in: MedlinePlus