Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic thymus has been reported previously. Here we show that Pax1 protein expression in thymic epithelial cells can be detected throughout thymic development and in the adult. Expression starts in the early endodermal epithelium lining the foregut region and includes the epithelium of the third pharyngeal pouch, a structure giving rise to part of the thymus epithelium. In early stages of thymus development a large proportion of thymus cells expresses Pax1. With increasing age, the proportion of Pax1-expressing cells is reduced and in the adult mouse only a small fraction of cortical thymic stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus epithelium is necessary for establishing the thymus microenvironment required for normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect not only the total size of the thymus but also the maturation of thymocytes. The number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+ immature and CD4+ mature thymocyte subsets. The expression levels of major thymocyte surface markers remains unchanged with the exception of Thy-1 which was found to be expressed at 3- to 4-fold higher levels.

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NKAP is required for T cell maturation and acquisition of functional competency

Journal of Experimental Medicine ◽

10.1084/jem.20101874 ◽

2011 ◽

Vol 208 (6) ◽

pp. 1291-1304 ◽

Cited By ~ 35

Author(s):

Fan-Chi Hsu ◽

Anthony G. Pajerowski ◽

Molly Nelson-Holte ◽

Rhianna Sundsbak ◽

Virginia Smith Shapiro

Keyword(s):

T Cells ◽

T Cell ◽

Conditional Knockout ◽

Cell Maturation ◽

Intrinsic Defect ◽

Thymic Development ◽

Cell Pool ◽

Single Positive ◽

Maturation Defect ◽

T Cell Maturation

Newly generated T cells are unable to respond to antigen/MHC. Rather, post-selection single-positive thymocytes must undergo T cell maturation to gain functional competency and enter the long-lived naive peripheral T cell pool. This process is poorly understood, as no gene specifically required for T cell maturation has been identified. Here, we demonstrate that loss of the transcriptional repressor NKAP results in a complete block in T cell maturation. In CD4-cre NKAP conditional knockout mice, thymic development including positive selection occurs normally, but there is a cell-intrinsic defect in the peripheral T cell pool. All peripheral naive CD4-cre NKAP conditional knockout T cells were found to be functionally immature recent thymic emigrants. This defect is not simply in cell survival, as the T cell maturation defect was not rescued by a Bcl-2 transgene. Thus, NKAP is required for T cell maturation and the acquisition of functional competency.

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An in vitro system of T cell maturation-effect of cytokines and of thymic epithelial cells ♦ 865

Pediatric Research ◽

10.1203/00006450-199804001-00886 ◽

1998 ◽

Vol 43 ◽

pp. 150-150

Author(s):

Athena P Kourtis ◽

Francis K Lee ◽

Christian Ibegbu ◽

Edmund Waller ◽

Andre J Nahmias

Keyword(s):

T Cell ◽

Epithelial Cells ◽

Cell Maturation ◽

Thymic Epithelial Cells ◽

In Vitro System ◽

T Cell Maturation

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Human CD4 Expression at the Late Single-Positive Stage of Thymic Development Supports T Cell Maturation and Peripheral Export in CD4-Deficient Mice

The Journal of Immunology ◽

10.4049/jimmunol.169.8.4347 ◽

2002 ◽

Vol 169 (8) ◽

pp. 4347-4353 ◽

Cited By ~ 1

Author(s):

Olivier Boyer ◽

Gilles Marodon ◽

José L. Cohen ◽

Laurence Lejeune ◽

Théano Irinopoulou ◽

...

Keyword(s):

T Cell ◽

Cell Maturation ◽

Thymic Development ◽

Single Positive ◽

T Cell Maturation ◽

Deficient Mice

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T Cell Homeostasis

Journal of Experimental Medicine ◽

10.1084/jem.194.5.591 ◽

2001 ◽

Vol 194 (5) ◽

pp. 591-600 ◽

Cited By ~ 108

Author(s):

Afonso R.M. Almeida ◽

José A.M. Borghans ◽

António A. Freitas

Keyword(s):

T Cell ◽

Cell Maturation ◽

Homeostatic Proliferation ◽

T Cell Homeostasis ◽

Double Positive ◽

Experimental Strategy ◽

Cell Compartments ◽

Thymus Cells ◽

The Relationship ◽

T Cell Maturation

We developed a novel experimental strategy to study T cell regeneration after bone marrow transplantation. We assessed the fraction of competent precursors required to repopulate the thymus and quantified the relationship between the size of the different T cell compartments during T cell maturation in the thymus. The contribution of the thymus to the establishment and maintenance of the peripheral T cell pools was also quantified. We found that the degree of thymus restoration is determined by the availability of competent precursors and that the number of double-positive thymus cells is not under homeostatic control. In contrast, the sizes of the peripheral CD4 and CD8 T cell pools are largely independent of the number of precursors and of the number of thymus cells. Peripheral “homeostatic” proliferation and increased export and/or survival of recent thymus emigrants compensate for reduced T cell production in the thymus. In spite of these reparatory processes, mice with a reduced number of mature T cells in the thymus have an increased probability of peripheral T cell deficiency, mainly in the naive compartment.

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Role of Prolactin in the Recovered T-Cell Development of Early Partially Decapitated Chicken Embryo

Developmental Immunology ◽

10.1155/1998/93086 ◽

1998 ◽

Vol 5 (3) ◽

pp. 183-195 ◽

Cited By ~ 10

Author(s):

J. Moreno ◽

A. Varas ◽

A. Vicente ◽

A. G. Zapata

Keyword(s):

T Cell ◽

Receptor Expression ◽

T Cell Subsets ◽

Cell Maturation ◽

Thymic Development ◽

Experimental Approaches ◽

Mammalian Immune System ◽

T Cell Maturation ◽

Control Sham

Although different experimental approaches have suggested certain regulation of the mammalian immune system by the neuroendocrine system, the precise factors involved in the process are largely unknown. In previous reports, we demonstrated important changes in the thymic development of chickens deprived of the major neuroendocrine centers by the removal of embryonic prosencephalon at 33-38 hr of incubation (DCx embryos) (Herradón et al., 1991; Moreno et al., 1995). In these embryos, there was a stopping of T-cell maturation that resulted in an accumulation of the most immature T-cell subsets (CD4-CD8-cells and CD4-CD81ocells) and, accordingly, in decreased numbers of DP (CD4+CD8+) thymocytes and mature CD3+TcRαβ+cells, but not CD3+TcRγδlymphocytes. In the present work, we restore the thymic histology as well as the percentage of distinct T-cell subsets of DCx embryos by supplying recombinant chicken prolactin, grafting of embryonic pituitary gland, or making cephalic chick-quail chimeras. The recovery was not, however, whole and the percentage of CD3+TcRαβthymocytes did not reach the normal values observed in 17-day-old control Sham-DCx embryos. The results are discussed on the basis of a key role for prolactin in chicken T-cell maturation. This hormone could regulate the transition of DN (CD4-CD8-) thymocytes to the DP (CD4+CD8+) cell compartment through its capacity for inducing IL-2 receptor expression on the former.

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