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Corrado Cilio

Professor

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Involvement of CCR9 at multiple stages of adult T lymphopoiesis.

Author

  • Marcus Svensson Frej
  • Jan Marsal
  • Heli Uronen-Hansson
  • Min Cheng
  • William Jenkinson
  • Corrado Cilio
  • Sten Eirik W Jacobsen
  • Ewa Sitnicka Quinn
  • Graham Anderson
  • William Agace

Summary, in English

The chemokine CCL25 is constitutively expressed in the thymus, and its receptor CCR9 is expressed on subsets of developing thymocytes. Nevertheless, the function of CCL25/CCR9 in adult thymopoiesis remains unclear. Here, we demonstrate that purified CCR9–/– hematopoietic stem cells are deficient in their ability to generate all major thymocyte subsets including double-negative 1 (DN1) cells in competitive transfers. CCR9–/– bone marrow contained normal numbers of lineage– Sca-1+c-kit+, common lymphoid progenitors, and lymphoid-primed multipotent progenitors (LMPP), and CCR9–/– LMPP showed similar T cell potential as their wild-type (WT) counterparts when cultured on OP9–{delta}-like 1 stromal cells. In contrast, early thymic progenitor and DN2 thymocyte numbers were reduced in the thymus of adult CCR9–/– mice. In fetal thymic organ cultures (FTOC), CCR9–/– DN1 cells were as efficient as WT DN1 cells in generating double-positive (DP) thymocytes; however, under competitive FTOC, CCR9–/– DP cell numbers were reduced significantly. Similarly, following intrathymic injection into sublethally irradiated recipients, CCR9–/– DN cells were out-competed by WT DN cells in generating DP thymocytes. Finally, in competitive reaggregation thymic organ cultures, CCR9–/– preselection DP thymocytes were disadvantaged significantly in their ability to generate CD4 single-positive (SP) thymocytes, a finding that correlated with a reduced ability to form TCR-MHC-dependent conjugates with thymic epithelial cells. Together, these results highlight a role for CCR9 at several stages of adult thymopoiesis: in hematopoietic progenitor seeding of the thymus, in the DN-DP thymocyte transition, and in the generation of CD4 SP thymocytes.

Department/s

  • Immunology
  • Stem Cell Center
  • Diabetes - Immunovirology

Publishing year

2008

Language

English

Pages

156-164

Publication/Series

Journal of Leukocyte Biology

Volume

83

Issue

1

Document type

Journal article

Publisher

John Wiley and Sons

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Immunology
  • Diabetes - Immunovirology

ISBN/ISSN/Other

  • ISSN: 1938-3673