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Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

Dong J, Chen Y, Xu X, Jin R, Teng F, Yan F, Tang H, Li P, Sun X, Li Y, Wu H, Zhang Y, Ge Q - PLoS ONE (2013)

Bottom Line: Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+) pre-RTEs in thymic perivascular space.Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs.The dendritic cell-driven Qa2 induction of CD4(+) pre-RTEs is independent of MHC class II and Aire molecules.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, Peking University Health Science Center, Beijing, China.

ABSTRACT
After a tightly regulated developmental program in the thymus, "mature" single positive (SP) thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs) are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+) pre-RTEs, a population of CD4(+) SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+) pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+) pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+) pre-RTEs is independent of MHC class II and Aire molecules.

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Comparison of the proliferation of pre-RTEs and naïve T cells in T-DC coculture system.Purified pre-RTEs (SP4 thymocytes) and naïve CD4+ T cells were labeled with CFSE and cultured with FLDCs at 10:1 ratio. The proliferation and CD44 upregulation were analyzed 4 days later. The fourth column displayed the T-DC coculture in the transwell system. T cells and DCs were separated by 0.4 µm transwell membrane. In the last column, Ly294002 was added to the T-DC coculture at 10 ng/ml. The numbers in the plot indicate the percentage of cells that diluted CFSE. The experiment was repeated for at least 3 times.
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pone-0056378-g005: Comparison of the proliferation of pre-RTEs and naïve T cells in T-DC coculture system.Purified pre-RTEs (SP4 thymocytes) and naïve CD4+ T cells were labeled with CFSE and cultured with FLDCs at 10:1 ratio. The proliferation and CD44 upregulation were analyzed 4 days later. The fourth column displayed the T-DC coculture in the transwell system. T cells and DCs were separated by 0.4 µm transwell membrane. In the last column, Ly294002 was added to the T-DC coculture at 10 ng/ml. The numbers in the plot indicate the percentage of cells that diluted CFSE. The experiment was repeated for at least 3 times.

Mentions: As dendritic cells (DCs) are essential in driving lymphopenia-induced naïve T cell proliferation, we tested whether pre-RTEs respond to DC-driven proliferation differently in vitro. Pre-RTEs and CD4+ naïve T cells were cultured in the presence of DCs and IL-7. Within 4 days, very little cells diluted the CFSE dye in naïve T cells whereas at least two cycles of cell division could be found in SP4 thymocytes (Fig. 5). The proliferation of pre-RTEs was not completely blocked by separating DCs and T cells with a transwell membrane, suggesting that cytokines produced by DCs play a role in driving T cell proliferation in this system. Inhibitors blocking PI3K could completely suppress the proliferation (Fig. 5).


Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

Dong J, Chen Y, Xu X, Jin R, Teng F, Yan F, Tang H, Li P, Sun X, Li Y, Wu H, Zhang Y, Ge Q - PLoS ONE (2013)

Comparison of the proliferation of pre-RTEs and naïve T cells in T-DC coculture system.Purified pre-RTEs (SP4 thymocytes) and naïve CD4+ T cells were labeled with CFSE and cultured with FLDCs at 10:1 ratio. The proliferation and CD44 upregulation were analyzed 4 days later. The fourth column displayed the T-DC coculture in the transwell system. T cells and DCs were separated by 0.4 µm transwell membrane. In the last column, Ly294002 was added to the T-DC coculture at 10 ng/ml. The numbers in the plot indicate the percentage of cells that diluted CFSE. The experiment was repeated for at least 3 times.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569422&req=5

pone-0056378-g005: Comparison of the proliferation of pre-RTEs and naïve T cells in T-DC coculture system.Purified pre-RTEs (SP4 thymocytes) and naïve CD4+ T cells were labeled with CFSE and cultured with FLDCs at 10:1 ratio. The proliferation and CD44 upregulation were analyzed 4 days later. The fourth column displayed the T-DC coculture in the transwell system. T cells and DCs were separated by 0.4 µm transwell membrane. In the last column, Ly294002 was added to the T-DC coculture at 10 ng/ml. The numbers in the plot indicate the percentage of cells that diluted CFSE. The experiment was repeated for at least 3 times.
Mentions: As dendritic cells (DCs) are essential in driving lymphopenia-induced naïve T cell proliferation, we tested whether pre-RTEs respond to DC-driven proliferation differently in vitro. Pre-RTEs and CD4+ naïve T cells were cultured in the presence of DCs and IL-7. Within 4 days, very little cells diluted the CFSE dye in naïve T cells whereas at least two cycles of cell division could be found in SP4 thymocytes (Fig. 5). The proliferation of pre-RTEs was not completely blocked by separating DCs and T cells with a transwell membrane, suggesting that cytokines produced by DCs play a role in driving T cell proliferation in this system. Inhibitors blocking PI3K could completely suppress the proliferation (Fig. 5).

Bottom Line: Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+) pre-RTEs in thymic perivascular space.Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs.The dendritic cell-driven Qa2 induction of CD4(+) pre-RTEs is independent of MHC class II and Aire molecules.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, Peking University Health Science Center, Beijing, China.

ABSTRACT
After a tightly regulated developmental program in the thymus, "mature" single positive (SP) thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs) are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+) pre-RTEs, a population of CD4(+) SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+) pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+) pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+) pre-RTEs is independent of MHC class II and Aire molecules.

Show MeSH
Related in: MedlinePlus