Quantitative and Qualitative Adjustment of Thymic T Cell Production by Clonal Expansion of Premigrant Thymocytes

Campion, Armelle Le; Lucas, Bruno; Dautigny, Nicole; Léaument, Sandrine; Vasseur, Florence; Pénit, Claude

doi:10.4049/jimmunol.168.4.1664

Cited by 21 publications

(17 citation statements)

References 53 publications

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“…It is also possible that an indeterminant number of SPCD4 and SPCD8 thymocytes may have incorporated BrdU at the DP stage. Previous studies of cell proliferation in the thymus of young adult mice have reported that SPCD4 and SPCD8 thymocytes undergo a late premigrant expansion phase, and that more than 50% of mature SP thymocytes replicate DNA in the 24 h prior to export from the postnatal murine thymus [26,27].…”

Section: Discussionmentioning

confidence: 99%

Cell death and thymic export during fetal life

et al. 2006

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In the fetus the peripheral T cell pool expands as the fetus grows, but the mechanisms that regulate T cell homeostasis during fetal life are unknown. Here, we show that the peripheral T cell pool in the sheep fetus is established by the export from the fetal thymus of twice as many CD8 + as CD4 + thymic emigrants every day. Clonal deletion of CD4 + thymocytes in the fetal thymus appeared to be more stringent than was the case for CD8+ thymocytes because only 1 in 35 single-positive CD4 (SPCD4) thymocytes was exported from the thymus whereas the majority (2/3) of the single-positive CD8 (SPCD8) thymocytes were exported from the fetal thymus each day. Furthermore, within the thymus, the number of apoptotic SPCD4 thymocytes was 40 times greater than the number of apoptotic SPCD8 thymocytes. A tissue-specific migration of CD8 + emigrants localizing in the spleen was also established in the fetus in contrast to CD4 + emigrants, which migrated randomly to spleen and LN.

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Section: Discussionmentioning

confidence: 99%

Cell death and thymic export during fetal life

et al. 2006

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“…In the latter case, we imposed equal selection fractions (␣ 4 ϭ ␣ 8 ) and equal export fractions ( f 4 ϭ f 8 ). We still found the best fit for our original model, where the CD4:CD8 ratios in the thymus and spleen are set, respectively, by the difference in thymic selection coefficient (␣ 4 and ␣ 8 ), and in fraction exported CD4 and CD8 thymocytes migrating to the spleen ( f 4 and f 8 ). This means that five times more CD4 than CD8 thymocytes are generated from DP cells (␣ 4 /␣ 8 ϭ 5).…”

Section: Selection In the Thymus And Export Rate To Peripherymentioning

confidence: 99%

Comprehensive Assessment and Mathematical Modeling of T Cell Population Dynamics and Homeostasis

Thomas‐Vaslin

Altes

Boer

et al. 2008

The Journal of Immunology

107

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Our current view of T cell differentiation and population dynamics is assembled from pieces of data obtained from separate experimental systems and is thus patchy. We reassessed homeostasis and dynamics of T cells 1) by generating a mathematical model describing the spatiotemporal features of T cell differentiation, and 2) by fitting this model to experimental data generated by disturbing T cell differentiation through transient depletion of dividing T cells in mice. This specific depletion was obtained by administration of ganciclovir to mice expressing the conditional thymidine kinase suicide gene in T cells. With this experimental approach, we could derive quantitative parameters describing the cell fluxes, residence times, and rates of import, export, proliferation, and death across cell compartments for thymocytes and recent thymic emigrants (RTEs). Among other parameters, we show that 93% of thymocytes produced before single-positive stages are eliminated through the selection process. Then, a postselection peripheral expansion of naive T cells contributes three times more to naive T cell production than the thymus, with half of the naive T cells consisting of dividing RTEs. Altogether, this work provides a quantitative population dynamical framework of thymocyte development, RTEs, and naive T cells.

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“…It has been shown by Campion et al (29) that premigrant thymocytes proliferate in a TCR-dependent manner before leaving the thymus. The loss of Egr1 could lead to decreased numbers of thymocytes emigrating the thymus because of reduced proliferation before exiting the thymus.…”

Section: Egr1mentioning

confidence: 99%

Control of Recent Thymic Emigrant Survival by Positive Selection Signals and Early Growth Response Gene 1

Schnell

Kersh

2005

The Journal of Immunology

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Early growth response gene 1 (Egr1) is a transcriptional regulator whose expression can be induced by multiple signals including the TCR. Egr1 has been shown to promote positive selection, but an investigation of its role in T cell homeostasis has not been reported. The possibility that similar signals control both positive selection and peripheral T cell homeostasis led us to investigate the role of Egr1 in the maintenance of peripheral T cells. We have found that on TCR transgenic backgrounds, Egr1-deficient mice have a reduction in their number of naive T cells. Although Egr1-deficient animals have a low percentage of mature thymocytes due to inefficient positive selection, the absolute number of mature thymocytes is only slightly reduced due to increased thymus size in Egr1-deficient mice. Despite possessing near normal numbers of mature thymocytes, we find that Egr1-deficient mice have poor accumulation of recent thymic emigrants (RTE) in the periphery. The poor accumulation of RTE in Egr1-deficient mice appears to originate from decreased survival of mature thymocytes and RTE, which we have observed both in vitro and in vivo. These findings suggest that an Egr1-mediated signal during positive selection promotes not only the production of single positive thymocytes, but also the survival of selected thymocytes until they can become established in the periphery.

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Quantitative and Qualitative Adjustment of Thymic T Cell Production by Clonal Expansion of Premigrant Thymocytes

Cited by 21 publications

References 53 publications

Cell death and thymic export during fetal life

Cell death and thymic export during fetal life

Comprehensive Assessment and Mathematical Modeling of T Cell Population Dynamics and Homeostasis

Control of Recent Thymic Emigrant Survival by Positive Selection Signals and Early Growth Response Gene 1

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