Extrathymic hemopoietic progenitors committed to T cell differentiation in the adult mouse.
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.
Arcangeli
Marie-Laure
ML
Institut National de la Sant é et de la Recherche Médicale Unit é 591, Institut Necker, Faculté de Médecine René Descartes Paris V, Paris, France.
Lancrin
Christophe
C
Lambolez
Florence
F
Cordier
Corinne
C
Schneider
Elke
E
Rocha
Benedita
B
Ezine
Sophie
S
D019264:Adoptive Transfer; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000378:metabolism; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D018960:Hyaluronan Receptors