Abstract

Cell number in the mouse thymus increases steadily during the first two weeks after birth. It then plateaus and begins to decline by seven weeks after birth. The factors governing these dramatic changes in cell production are not well understood. The data herein correlate levels of High mobility group A 2 protein (Hmga2) expression with these temporal changes in thymopoiesis. Hmga2 is expressed at high levels in murine fetal and neonatal early T cell progenitors (ETP), which are the most immature intrathymic precursors, and becomes almost undetectable in these progenitors after 5 weeks of age. Hmga2 expression is critical for the initial, exponential expansion of thymopoiesis, as Hmga2 deficient mice have a deficit of ETPs within days after birth, and total thymocyte number is repressed compared to wild type littermates. Finally, our data raise the possibility that similar events occur in humans, because Hmga2 expression is high in human fetal thymic progenitors and falls in these cells during early infancy.

Highlights

  • The rate of T cell production in the murine thymus varies considerably at different stages of life

  • Because reductions in High mobility group A 2 protein (Hmga2) expression in hematopoietic stem cells (HSCs) are evident in young adult mice [4], we refocused our studies from aging per se to determine the precise time at which declines occur in early T cell progenitors (ETP)

  • These analyses demonstrated that there is a decline in Hmga2 expression in ETP following the neonatal period

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Summary

Introduction

The rate of T cell production in the murine thymus varies considerably at different stages of life. One of the most dramatic fluctuations occurs between fetal and young adult life. The key feature of this stage of development is the increase in thymus cellularity that is critical for generating the high number of thymocytes that colonize secondary lymphoid tissues and establishing the T cell repertoire. Thymus cell number increases exponentially through the first two weeks after birth. It plateaus, and thymopoiesis begins to decline by seven weeks after.

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