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Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus.
Nature. 2005 Aug 25; 436(7054):1181-5.Nat

Abstract

Hassall's corpuscles-first described in the human thymus over 150 years ago-are groups of epithelial cells within the thymic medulla. The physical nature of these structures differs between mammalian species. Although Hassall's corpuscles have been proposed to act in both the removal of apoptotic thymocytes and the maturation of developing thymocytes within the thymus, the function of Hassall's corpuscles has remained an enigma. Here we report that human Hassall's corpuscles express thymic stromal lymphopoietin (TSLP). Human TSLP activates thymic CD11c-positive dendritic cells to express high levels of CD80 and CD86. These TSLP-conditioned dendritic cells are then able to induce the proliferation and differentiation of CD4(+)CD8(-)CD25(-) thymic T cells into CD4(+)CD25(+)FOXP3(+) (forkhead box P3) regulatory T cells. This induction depends on peptide-major histocompatibility complex class II interactions, and the presence of CD80 and CD86, as well as interleukin 2. Immunohistochemistry studies reveal that CD25(+)CTLA4(+) (cytotoxic T-lymphocyte-associated protein 4) regulatory T cells associate in the thymic medulla with activated or mature dendritic cells and TSLP-expressing Hassall's corpuscles. These findings suggest that Hassall's corpuscles have a critical role in dendritic-cell-mediated secondary positive selection of medium-to-high affinity self-reactive T cells, leading to the generation of CD4(+)CD25(+) regulatory T cells within the thymus.

Authors+Show Affiliations

Department of Immunology and Center for Cancer Immunology Research, The University of Texas, M. D. Anderson Cancer Center, 7455 Fannin Street, Houston, Texas 77054, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16121185

Citation

Watanabe, Norihiko, et al. "Hassall's Corpuscles Instruct Dendritic Cells to Induce CD4+CD25+ Regulatory T Cells in Human Thymus." Nature, vol. 436, no. 7054, 2005, pp. 1181-5.
Watanabe N, Wang YH, Lee HK, et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature. 2005;436(7054):1181-5.
Watanabe, N., Wang, Y. H., Lee, H. K., Ito, T., Wang, Y. H., Cao, W., & Liu, Y. J. (2005). Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature, 436(7054), 1181-5.
Watanabe N, et al. Hassall's Corpuscles Instruct Dendritic Cells to Induce CD4+CD25+ Regulatory T Cells in Human Thymus. Nature. 2005 Aug 25;436(7054):1181-5. PubMed PMID: 16121185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. AU - Watanabe,Norihiko, AU - Wang,Yi-Hong, AU - Lee,Heung Kyu, AU - Ito,Tomoki, AU - Wang,Yui-Hsi, AU - Cao,Wei, AU - Liu,Yong-Jun, PY - 2005/04/01/received PY - 2005/06/06/accepted PY - 2005/8/27/pubmed PY - 2005/9/9/medline PY - 2005/8/27/entrez SP - 1181 EP - 5 JF - Nature JO - Nature VL - 436 IS - 7054 N2 - Hassall's corpuscles-first described in the human thymus over 150 years ago-are groups of epithelial cells within the thymic medulla. The physical nature of these structures differs between mammalian species. Although Hassall's corpuscles have been proposed to act in both the removal of apoptotic thymocytes and the maturation of developing thymocytes within the thymus, the function of Hassall's corpuscles has remained an enigma. Here we report that human Hassall's corpuscles express thymic stromal lymphopoietin (TSLP). Human TSLP activates thymic CD11c-positive dendritic cells to express high levels of CD80 and CD86. These TSLP-conditioned dendritic cells are then able to induce the proliferation and differentiation of CD4(+)CD8(-)CD25(-) thymic T cells into CD4(+)CD25(+)FOXP3(+) (forkhead box P3) regulatory T cells. This induction depends on peptide-major histocompatibility complex class II interactions, and the presence of CD80 and CD86, as well as interleukin 2. Immunohistochemistry studies reveal that CD25(+)CTLA4(+) (cytotoxic T-lymphocyte-associated protein 4) regulatory T cells associate in the thymic medulla with activated or mature dendritic cells and TSLP-expressing Hassall's corpuscles. These findings suggest that Hassall's corpuscles have a critical role in dendritic-cell-mediated secondary positive selection of medium-to-high affinity self-reactive T cells, leading to the generation of CD4(+)CD25(+) regulatory T cells within the thymus. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/16121185/Hassall's_corpuscles_instruct_dendritic_cells_to_induce_CD4+CD25+_regulatory_T_cells_in_human_thymus_ L2 - https://doi.org/10.1038/nature03886 DB - PRIME DP - Unbound Medicine ER -