Immunohistological analysis of immigration of thymocyte-precursors into the thymus: Evidence for immigration of peripheral T cells into the thymic medulla

Hirokawa, Katsuíku; Utsuyama, Masanori; Sado, Toshihiko

doi:10.1016/0008-8749(89)90232-3

Cited by 46 publications

(35 citation statements)

References 13 publications

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“…Inmost experiments, the approach used was to inject young (6-10 wk) mice with Thy-1-marked T cells intravenously and then search for donor cells in the host thymus and other organs using FACS® analysis . B6 (H-2b, Thy-1 .2) T cells were transferred to B6 (5)(6) mo) donor mice in initial experiments . Two experiments with these donors led to significant thymic homing, i .e., -0.2% of Jlld-cells (data not shown) .…”

Section: Resultsmentioning

confidence: 99%

“…This notion rests on the assumption that lymphocyte traffic from the thymus is strictly unidirectional . However, there are a number of reports that T cell lines or mature lymphocytes harvested from the secondary lymphoid organs are able to localize in the thymus in appreciable numbers after intravenous injection (3)(4)(5)(6) . These cells localize largely in the medulla .…”

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confidence: 99%

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Reentry of T cells to the adult thymus is restricted to activated T cells.

Agus

Surh

Sprent

1991

The Journal of Experimental Medicine

248

165

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SummaryTo seek information on the capacity of mature T cells to migrate to the thymus, mice were injected with Thy-l-marked populations enriched for resting T cells or T blast cells ; localization of the donor cells in the host thymus was assessed by staining cryostat sections of thymus and by FACS® analysis of cell suspensions . With injection of purified resting T cells, thymic homing was extremely limited, even with injection of large doses of cells. By contrast, in vivo generated T blast cells migrated to the thymus in substantial numbers . Thymic homing by T blasts was >50-fold more efficient than with resting T cells . Blast cells localized largely in the medulla and remained in the thymus for at least 1 mo post-transfer. Interestingly, localization of T blasts in the thymus was 10-fold higher in irradiated hosts than normal hosts . Thymic homing was especially prominent in mice injected with T blasts incubated in vitro with the DNA precursor, 125 I-5-iodo-2'deoxyuridine ( 125IDUR); with transfer of 125IDURlabeled blasts to irradiated hosts, up to 5% of the injected counts localized in the host thymus. These data suggest that thymic homing by T blasts might be largely restricted to cells in S phase. The physiological significance of blast cell entry to the thymus is unclear. The possibility that these cells participate in intrathymic tolerance induction is discussed.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Reentry of T cells to the adult thymus is restricted to activated T cells.

Agus

Surh

Sprent

1991

The Journal of Experimental Medicine

248

165

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“…It is unknown what triggers the leakiness of aged thymic tissue, but young thymic lobes maintain the barrier to naïve T cells even after thymic atrophy is induced by irradiation and cortisone injection (20). Activated allogeneic T cells reside in the medulla of the young thymus (20,26,27) and have been shown to induce alloantigen-specific tolerance (21,28). It has also been suggested that activated T cells persisting in the thymus may serve as a repository of memory in the young adult (18,19).…”

Section: Discussionmentioning

confidence: 99%

Thymic output in aged mice

Hale

Boursalian

Turk

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

276

295

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Using GFP to mark recent thymic emigrants (RTEs) in mice carrying a GFP transgene driven by the recombination-activating gene 2 promoter, we demonstrate that RTEs are readily detectable even in 2-year-old mice, despite the fact that the proportion of the peripheral T cell pool comprised of RTEs declines with age. Although the number of RTEs decreases after reaching a peak at 6 weeks of age, thymic output as a function of thymic size is surprisingly age-independent. The CD4:CD8 ratio of RTEs declines with age, partly because of a striking decrease in steady-state proliferation of CD4 ؉ RTEs in older mice. RTEs in aged mice undergo phenotypic maturation in the lymphoid periphery with delayed kinetics compared with young mice. RTEs from aged mice secrete less IL-2, proliferate less well, and achieve only weak expression of earlyactivation markers compared with more mature naïve peripheral T cells from the same mice. The proportion of GFP ؊ cells in the CD4 ؉ and CD8 ؉ thymic compartments increases with age, partly as a result of leakiness in the aged thymus, allowing reentry of naïve peripheral T cells.aging ͉ recent thymic emigrants ͉ T cell development M aintenance of the peripheral T cell population throughout life depends on balancing the influx of recent thymic emigrants (RTEs) with the homeostatic regulation of mature peripheral T cells. Although T cell numbers can be sustained by homeostatic proliferation of peripheral T cells after lymphocyte depletion, the thymus is essential for maintaining a diverse antigen receptor repertoire and a substantial pool of naïve peripheral T cells. Hallmarks of the aging immune system include thymic involution, enhanced contribution of memory cells to the peripheral T cell pool, and striking clonal expansions among both CD4 and CD8 T cell populations (reviewed in refs. 1 and 2). These phenomena are interrelated, because shrinkage of the thymus limits the number of newly exported T cells, triggering the gradual decline in the naïve T cell pool, which in turn likely contributes to the expansion of select memory phenotype T cells.Understanding the contribution of thymic output to the peripheral T cell pool requires identification of RTEs as a population distinct from the bulk of naïve and previously activated peripheral T cells. Over the years, this distinction has been achieved in mice by identifying RTEs that have originated from thymocytes labeled by BrdU (3) or intrathymic injection of FITC (4, 5) by following a wave of thymocyte differentiation and egress from thymic lobes transplanted into congenic hosts (6, 7) and in mice and humans by using T cell receptor (TCR) rearrangement excision circles to identify cells that have not proliferated since rearranging antigen receptor genes (8-13). Although highly useful, these techniques suffer serious disadvantages, including the short time frame over which RTEs can be observed (4-7), the trauma inherent in the labeling technique and its potential to alter thymic output (4-7), the inherent inaccuracy of the tag itself (3,(8)(9)(10)...

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“…Several surface markers have been described that are expressed on medullary epithelial cells (36,39,(47)(48)(49)(50). The Ab designated 29 recognizes a subpopulation of TEC thought to represent stromal cells bearing features of "activated" cells (36,51).…”

Section: Aire Is Expressed In the Medulla And At The Corticomedullarymentioning

confidence: 99%

Normal Thymic Architecture and Negative Selection Are Associated with Aire Expression, the Gene Defective in the Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)

Žuklys

Balc̆iūnaite

Agarwal

et al. 2000

The Journal of Immunology

234

159

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T cell development is tightly controlled by thymic stromal cells. Alterations in stromal architecture affect T cell maturation and the development of self-tolerance. The monogenic autoimmune syndrome APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy) is characterized by the loss of self-tolerance to multiple organs. Although mutations in the autoimmune regulator (AIRE) gene are responsible for this disease, the function of AIRE is not known. Here we report on the spatial and temporal pattern of murine Aire expression during thymic ontogeny and T cell selection. Early during development, thymic Aire transcription is critically dependent on RelB and occurs in epithelial cells in response to lymphocyte-mediated signals. In adult tissue, Aire expression is confined to the medulla and the corticomedullary junction, where it is modulated by thymocytes undergoing negative selection. Aire may determine thymic stromal organization and with it the induction of self-tolerance.

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Immunohistological analysis of immigration of thymocyte-precursors into the thymus: Evidence for immigration of peripheral T cells into the thymic medulla

Cited by 46 publications

References 13 publications

Reentry of T cells to the adult thymus is restricted to activated T cells.

Reentry of T cells to the adult thymus is restricted to activated T cells.

Thymic output in aged mice

Normal Thymic Architecture and Negative Selection Are Associated with Aire Expression, the Gene Defective in the Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)

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