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Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47.

Bain G, Quong MW, Soloff RS, Hedrick SM, Murre C - J. Exp. Med. (1999)

Bottom Line: Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47.Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells.Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of California, San Diego, La Jolla, California 92093, USA.

ABSTRACT
The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection.

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Appearance of DP cells in the periphery of E47-deficient/ H-Y transgenic mice. 6-wk-old H-Y transgenic mice of the indicated E47 genotype were analyzed by three-color flow cytometry for the expression of CD4, CD8, and either HSA (B) or TCR-α/β (C). The CD4 versus CD8 profiles for the thymocytes (top panels) and splenocytes (bottom panels) are shown (A), and the numbers in each quadrant indicate the percentage of cells in that population. The boxed regions in the CD4 versus CD8 plots (a–e) indicate the analysis gates used to define the populations analyzed in B and C. In the histogram plots (B and C), the lettered arrows indicate the staining pattern for the corresponding boxed populations in A. To make comparisons clearer, the histograms were plotted in pairs to compare the peripheral DP population with the thymic DP population (left panels) and with the SP populations (right panels).
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Figure 5: Appearance of DP cells in the periphery of E47-deficient/ H-Y transgenic mice. 6-wk-old H-Y transgenic mice of the indicated E47 genotype were analyzed by three-color flow cytometry for the expression of CD4, CD8, and either HSA (B) or TCR-α/β (C). The CD4 versus CD8 profiles for the thymocytes (top panels) and splenocytes (bottom panels) are shown (A), and the numbers in each quadrant indicate the percentage of cells in that population. The boxed regions in the CD4 versus CD8 plots (a–e) indicate the analysis gates used to define the populations analyzed in B and C. In the histogram plots (B and C), the lettered arrows indicate the staining pattern for the corresponding boxed populations in A. To make comparisons clearer, the histograms were plotted in pairs to compare the peripheral DP population with the thymic DP population (left panels) and with the SP populations (right panels).

Mentions: In addition to the increased production of CD8 SP cells, female E47−/−;H-Y mice displayed an aberrant population of T cells in the peripheral lymphoid organs that expressed high levels of CD8 and intermediate to high levels of CD4 (Fig. 4 A and Fig. 5 A). To examine whether the peripheral DP (PDP) population expressed markers characteristic of mature T lineage cells, we analyzed this population for the expression of TCR-α/β and HSA. The PDP cells expressed HSA at a level similar to normal SP thymocytes, and significantly lower than the level of expression on thymic DP cells (Fig. 5 B). However, the expression of HSA on the PDP population is significantly higher than the level observed on normal SP peripheral T cells (Fig. 5 B, right). TCR-α/β expression on the PDP cells was identical to that of the mature SP T cells, with all of the cells expressing uniformly high levels of TCR (Fig. 5 C). Taken together, the data suggest that the PDP cells in the E47−/−;H-Y mice are positively selected T lineage cells that fail to complete maturation before exiting to the periphery.


Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47.

Bain G, Quong MW, Soloff RS, Hedrick SM, Murre C - J. Exp. Med. (1999)

Appearance of DP cells in the periphery of E47-deficient/ H-Y transgenic mice. 6-wk-old H-Y transgenic mice of the indicated E47 genotype were analyzed by three-color flow cytometry for the expression of CD4, CD8, and either HSA (B) or TCR-α/β (C). The CD4 versus CD8 profiles for the thymocytes (top panels) and splenocytes (bottom panels) are shown (A), and the numbers in each quadrant indicate the percentage of cells in that population. The boxed regions in the CD4 versus CD8 plots (a–e) indicate the analysis gates used to define the populations analyzed in B and C. In the histogram plots (B and C), the lettered arrows indicate the staining pattern for the corresponding boxed populations in A. To make comparisons clearer, the histograms were plotted in pairs to compare the peripheral DP population with the thymic DP population (left panels) and with the SP populations (right panels).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2195738&req=5

Figure 5: Appearance of DP cells in the periphery of E47-deficient/ H-Y transgenic mice. 6-wk-old H-Y transgenic mice of the indicated E47 genotype were analyzed by three-color flow cytometry for the expression of CD4, CD8, and either HSA (B) or TCR-α/β (C). The CD4 versus CD8 profiles for the thymocytes (top panels) and splenocytes (bottom panels) are shown (A), and the numbers in each quadrant indicate the percentage of cells in that population. The boxed regions in the CD4 versus CD8 plots (a–e) indicate the analysis gates used to define the populations analyzed in B and C. In the histogram plots (B and C), the lettered arrows indicate the staining pattern for the corresponding boxed populations in A. To make comparisons clearer, the histograms were plotted in pairs to compare the peripheral DP population with the thymic DP population (left panels) and with the SP populations (right panels).
Mentions: In addition to the increased production of CD8 SP cells, female E47−/−;H-Y mice displayed an aberrant population of T cells in the peripheral lymphoid organs that expressed high levels of CD8 and intermediate to high levels of CD4 (Fig. 4 A and Fig. 5 A). To examine whether the peripheral DP (PDP) population expressed markers characteristic of mature T lineage cells, we analyzed this population for the expression of TCR-α/β and HSA. The PDP cells expressed HSA at a level similar to normal SP thymocytes, and significantly lower than the level of expression on thymic DP cells (Fig. 5 B). However, the expression of HSA on the PDP population is significantly higher than the level observed on normal SP peripheral T cells (Fig. 5 B, right). TCR-α/β expression on the PDP cells was identical to that of the mature SP T cells, with all of the cells expressing uniformly high levels of TCR (Fig. 5 C). Taken together, the data suggest that the PDP cells in the E47−/−;H-Y mice are positively selected T lineage cells that fail to complete maturation before exiting to the periphery.

Bottom Line: Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47.Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells.Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of California, San Diego, La Jolla, California 92093, USA.

ABSTRACT
The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection.

Show MeSH
Related in: MedlinePlus