Checkpoints in the Development of Thymic Cortical Epithelial Cells

Saba Shakib,Sonia M Parnell,Guillaume E Desanti,Eric J Jenkinson,Graham Anderson,William E Jenkinson

doi:10.4049/jimmunol.182.1.130

Abstract

In the thymus, interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells. Despite the importance of cortical (cTEC) and medullary (mTEC) thymic epithelial cells in fostering T cell production, events in TEC development are still unclear. Although precursor-product relationships during mTEC development have been reported, and some genetic regulators of mTEC development have been identified, stages in cTEC development occurring downstream of recently identified bipotent cTEC/mTEC progenitors remain poorly defined. In this study, we combine analysis of differentiation, proliferation, and gene expression of TECs in the murine thymus, that has enabled us to identify cTEC progenitors, define multiple stages in cTEC development, and identify novel checkpoints in development of the cTEC lineage. We show an essential requirement for FoxN1 in the initial development of cTEC from bipotent progenitors, and demonstrate a stage-specific requirement for CD4(-)8(-) thymocytes in later stages of cTEC development. Collectively, our data establish a program of cTEC development that should provide insight into the formation and function of the thymic cortex for T cell development.

Highlights

Interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells
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By gating on EpCAMϩ thymic epithelial cells (TECs), and in contrast to the presence of a large population of CD205ϩ cTEC present in fetal thymic organ culture (FTOC), Fig. 1a shows that a small but detectable EpCAM1ϩCD205ϩ subset of TEC is present at E12 of gestation, with the frequency of these cells increasing during thymus ontogeny

Summary

Introduction

Interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells. We have dissected the stages of cTEC development beginning with bipotent TEC progenitors and culminating in the generation of mature cTEC expressing high levels of MHC class II.

Results

Conclusion