Extrathymic hemopoietic progenitors committed to T cell differentiation in the adult mouse

J Immunol. 2005 Feb 15;174(4):1980-8. doi: 10.4049/jimmunol.174.4.1980.


The role of the thymus in T cell commitment of hemopoietic precursor is yet controversial. We previously identified a major T cell progenitor activity in precursor cells isolated from bone marrow-derived spleen colonies. In this study, we characterize the properties of these pre-T cells. We demonstrate that they have unique phenotype and can be generated in a total absence of any thymic influence. Indeed, even when studied at the single-cell level, extrathymic T cell-committed precursors express T cell-specific genes. Moreover, these cells are not committed to a particular T cell differentiation pathway because they can generate both extrathymic CD8alphaalpha+ intraepithelial lymphocytes and thymus-derived conventional thymocytes. We also compared these pre-T cells with fully T cell-committed thymic progenitors. When tested in vitro or by direct intrathymic transfer, these cells have a low clonogenic activity. However, after i.v. transfer, thymus repopulation is efficient and these precursors generate very high numbers of peripheral T cells. These results suggest the existence of extra steps of pre-T cell maturation that improve thymus reconstitution capacity and that can be delivered even after full T cell commitment. Consequently, our studies identify a source of extrathymic progenitors that will be helpful in defining the role of the thymus in the earliest steps of T cell differentiation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD3 Complex / metabolism
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Female
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology*
  • Hyaluronan Receptors / metabolism
  • Immunophenotyping
  • Injections, Intravenous
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Radiation Chimera
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / cytology*
  • Thymus Gland / cytology*
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Thymus Gland / transplantation


  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Hyaluronan Receptors