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Constitutive activation of integrin alpha 4 beta 1 defines a unique stage of human thymocyte development

Academic Article
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Overview

authors

  • Salomon, Daniel
  • Mojcik, C. F.
  • Chang, A. C.
  • Wadsworth, S.
  • Adams, D. H.
  • Coligan, J. E.
  • Shevach, E. M.

publication date

  • May 1994

journal

  • Journal of Experimental Medicine  Journal

abstract

  • Our understanding of thymocyte development and of the positive and negative selection events involved in shaping the repertoire of mature T lymphocytes has been greatly facilitated by the use of transgenic and gene knockout animals. Much less is known about the factors that control the homing and population of the thymus by T cell precursors and the subsequent migration of developing thymocytes through the thymic architecture. As the integrins represent a candidate group of cell surface receptors that may regulate thymocyte development, we have analyzed the expression and function of alpha 4 beta 1 and alpha 5 beta 1 on human thymocytes. A major portion of double positive (CD4+ CD8+) human thymocytes express alpha 4 beta 1 in a constitutively active form and adhere to fibronectin and vascular cell adhesion molecule 1. alpha 4 beta 1 expression is similar on adherent and nonadherent populations, thus, activity reflects the receptor state and not simple expression. The adherent cells are immature, expressing high levels of CD4/CD8 and low levels of CD3 and CD69. In contrast, nonadherent cells possess the phenotype of thymocytes after positive selection, expressing intermediate levels of CD4 and/or CD8 and high levels of CD3 and CD69. The adherent population fails to respond to activation with anti-CD3 and fibronectin, whereas nonadherents exhibit an alpha 5 beta 1-dependent proliferation. Differential regulation of alpha 4 beta 1 and alpha 5 beta 1 receptors may provide a mechanism controlling cellular traffic, differentiation, and positive selection of thymocytes.

subject areas

  • Antibodies
  • Antigens, CD
  • Antigens, CD3
  • Antigens, CD4
  • Antigens, CD8
  • Antigens, Differentiation, T-Lymphocyte
  • Cell Adhesion
  • Cell Division
  • Child, Preschool
  • Fibronectins
  • Humans
  • Infant
  • Integrin alpha4beta1
  • Integrins
  • Lectins, C-Type
  • Stem Cells
  • T-Lymphocyte Subsets
  • Thymus Gland
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Identity

PubMed Central ID

  • PMC2191505

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.179.5.1573

PubMed ID

  • 8163937
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Additional Document Info

start page

  • 1573

end page

  • 1584

volume

  • 179

issue

  • 5

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