Human Stem Cell-Derived Thymic Epithelial Cells Enhance Human T Cell Development in a Xenogeneic Thymus.

Hematopoietic stem cells (HSCs) reside in distinct sites throughout fetal and adult life and give rise to all cells of the hematopoietic system. Because of their multipotency, HSCs are capable of curing a wide variety of blood disorders through hematopoietic stem cell transplantation (HSCT). However, due to HSC heterogeneity, site-specific ontogeny and current limitations in generating and expanding HSCs in vitro, their broad use in clinical practice remains challenging. To assess HSC multipotency, evaluation of their capacity to generate T lymphocytes has been regarded as a valid read-out. Several in vitro models of T cell development have been established which are able to induce T-lineage differentiation from different hematopoietic precursors, although with variable efficiency. Here, we review the potential of human HSCs from various sources to generate T-lineage cells using these different models in order to address the use of both HSCs and T cell precursors in the clinic.

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Corrigendum: Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development

Frontiers in Immunology ◽

10.3389/fimmu.2020.628464 ◽

2020 ◽

Vol 11 ◽

Author(s):

Hong-Xia Wang ◽

Wenrong Pan ◽

Lei Zheng ◽

Xiao-Ping Zhong ◽

Liang Tan ◽

...

Keyword(s):

T Cell ◽

Epithelial Cells ◽

T Cell Development ◽

Cell Development ◽

Thymic Epithelial Cells

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Foxn1 maintains thymic epithelial cells to support T-cell development via mcm2 in zebrafish

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1217021110 ◽

2012 ◽

Vol 109 (51) ◽

pp. 21040-21045 ◽

Cited By ~ 20

Author(s):

D. Ma ◽

L. Wang ◽

S. Wang ◽

Y. Gao ◽

Y. Wei ◽

...

Keyword(s):

T Cell ◽

Epithelial Cells ◽

T Cell Development ◽

Cell Development ◽

Thymic Epithelial Cells

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Prss16 Is Not Required for T-Cell Development

Molecular and Cellular Biology ◽

10.1128/mcb.25.2.789-796.2005 ◽

2005 ◽

Vol 25 (2) ◽

pp. 789-796 ◽

Cited By ~ 10

Author(s):

Saijai Cheunsuk ◽

Zhe-Xiong Lian ◽

Guo-Xiang Yang ◽

M. Eric Gershwin ◽

Jeffrey R. Gruen ◽

...

Keyword(s):

T Cell ◽

Epithelial Cells ◽

Mhc Class Ii ◽

T Cell Development ◽

Surface Expression ◽

Class Ii ◽

Cell Development ◽

Thymic Epithelial Cells ◽

Wild Type ◽

Thymic Development

ABSTRACT PRSS16 is a serine protease expressed exclusively in cortical thymic epithelial cells (cTEC) of the thymus, suggesting that it plays a role in the processing of peptide antigens during the positive selection of T cells. Moreover, the human PRSS16 gene is encoded in a region near the class I major histocompatibility complex (MHC) that has been linked to type 1 diabetes mellitus susceptibility. The mouse orthologue Prss16 is conserved in genetic structure, sequence, and pattern of expression. To study the role of Prss16 in thymic development, we generated a deletion mutant of Prss16 and characterized T-lymphocyte populations and MHC class II expression on cortical thymic epithelial cells. Prss16-deficient mice develop normally, are fertile, and show normal thymic morphology, cellularity, and anatomy. The total numbers and frequencies of thymocytes and splenic T-cell populations did not differ from those of wild-type controls. Surface expression of MHC class II on cTEC was also similar in homozygous mutant and wild-type animals, and invariant chain degradation was not impaired by deletion of Prss16. These findings suggest that Prss16 is not required for quantitatively normal T-cell development.

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Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells

Blood ◽

10.1182/blood-2006-10-049767 ◽

2007 ◽

Vol 109 (9) ◽

pp. 3803-3811 ◽

Cited By ~ 124

Author(s):

Simona W. Rossi ◽

Lukas T. Jeker ◽

Tomoo Ueno ◽

Sachiyo Kuse ◽

Marcel P. Keller ◽

...

Keyword(s):

T Cell ◽

Growth Factor ◽

Epithelial Cells ◽

Stromal Cells ◽

Keratinocyte Growth Factor ◽

T Cell Development ◽

Cell Development ◽

Thymic Epithelial Cells ◽

Thymic Stromal Cells ◽

Architectural Organization

Abstract The systemic administration of keratinocyte growth factor (KGF) enhances T-cell lymphopoiesis in normal mice and mice that received a bone marrow transplant. KGF exerts protection to thymic stromal cells from cytoablative conditioning and graft-versus-host disease–induced injury. However, little is known regarding KGF's molecular and cellular mechanisms of action on thymic stromal cells. Here, we report that KGF induces in vivo a transient expansion of both mature and immature thymic epithelial cells (TECs) and promotes the differentiation of the latter type of cells. The increased TEC numbers return within 2 weeks to normal values and the microenvironment displays a normal architectural organization. Stromal changes initiate an expansion of immature thymocytes and permit regular T-cell development at an increased rate and for an extended period of time. KGF signaling in TECs activates both the p53 and NF-κB pathways and results in the transcription of several target genes necessary for TEC function and T-cell development, including bone morphogenetic protein 2 (BMP2), BMP4, Wnt5b, and Wnt10b. Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis.

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