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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 lymphopenia-induced proliferation of pre-RTEs and naïve T cells.Purified SP4 thymocytes, and CD4+ naïve T cells from lymph nodes of C57BL/6 mice were labeled with CFSE and adoptively transferred into sub-lethally irradiated (600 rads) adult C57BL/6 mice (A and B) or unirradiated 9-day old C57BL/6 mice (C). Donor T cells from lymph nodes (LN) of the hosts were analyzed for CD44 expression and CFSE dilution (proliferation) 4 days (irradiated mice) and 14 days (unirradiated young mice) later. The numbers in the plot display the percentage of cells diluted CFSE (A) or CD44hi (upper) and CD44lo (lower) cells that diluted CFSE (B-D). The experiments were repeated for 3 times.
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pone-0056378-g004: Comparison of lymphopenia-induced proliferation of pre-RTEs and naïve T cells.Purified SP4 thymocytes, and CD4+ naïve T cells from lymph nodes of C57BL/6 mice were labeled with CFSE and adoptively transferred into sub-lethally irradiated (600 rads) adult C57BL/6 mice (A and B) or unirradiated 9-day old C57BL/6 mice (C). Donor T cells from lymph nodes (LN) of the hosts were analyzed for CD44 expression and CFSE dilution (proliferation) 4 days (irradiated mice) and 14 days (unirradiated young mice) later. The numbers in the plot display the percentage of cells diluted CFSE (A) or CD44hi (upper) and CD44lo (lower) cells that diluted CFSE (B-D). The experiments were repeated for 3 times.

Mentions: We next compared the capability of lymphopenia-induced proliferation between pre-RTEs and lymph node-resident CD4+ naïve T cells. Both SP3 and SP4 pre-RTEs proliferated significantly faster than naïve T cells in the adult mice that received sub-lethal dose of irradiation (Fig. 4A and 4B). Similar results were obtained in the hosts of nine-day old young mice in which the peripheral T cell pool was not yet completely filled (Fig. 4C). This is consistent with the findings by Houston, et al. that RTEs proliferated faster than naïve T cells in lymphopenic condition [30].


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 lymphopenia-induced proliferation of pre-RTEs and naïve T cells.Purified SP4 thymocytes, and CD4+ naïve T cells from lymph nodes of C57BL/6 mice were labeled with CFSE and adoptively transferred into sub-lethally irradiated (600 rads) adult C57BL/6 mice (A and B) or unirradiated 9-day old C57BL/6 mice (C). Donor T cells from lymph nodes (LN) of the hosts were analyzed for CD44 expression and CFSE dilution (proliferation) 4 days (irradiated mice) and 14 days (unirradiated young mice) later. The numbers in the plot display the percentage of cells diluted CFSE (A) or CD44hi (upper) and CD44lo (lower) cells that diluted CFSE (B-D). The experiments were repeated for 3 times.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0056378-g004: Comparison of lymphopenia-induced proliferation of pre-RTEs and naïve T cells.Purified SP4 thymocytes, and CD4+ naïve T cells from lymph nodes of C57BL/6 mice were labeled with CFSE and adoptively transferred into sub-lethally irradiated (600 rads) adult C57BL/6 mice (A and B) or unirradiated 9-day old C57BL/6 mice (C). Donor T cells from lymph nodes (LN) of the hosts were analyzed for CD44 expression and CFSE dilution (proliferation) 4 days (irradiated mice) and 14 days (unirradiated young mice) later. The numbers in the plot display the percentage of cells diluted CFSE (A) or CD44hi (upper) and CD44lo (lower) cells that diluted CFSE (B-D). The experiments were repeated for 3 times.
Mentions: We next compared the capability of lymphopenia-induced proliferation between pre-RTEs and lymph node-resident CD4+ naïve T cells. Both SP3 and SP4 pre-RTEs proliferated significantly faster than naïve T cells in the adult mice that received sub-lethal dose of irradiation (Fig. 4A and 4B). Similar results were obtained in the hosts of nine-day old young mice in which the peripheral T cell pool was not yet completely filled (Fig. 4C). This is consistent with the findings by Houston, et al. that RTEs proliferated faster than naïve T cells in lymphopenic condition [30].

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