Lymphoid Gene Upregulation on Circulating Progenitors Participates in Their T-Lineage Commitment.
J Immunol
; 195(1): 156-65, 2015 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-26026063
ABSTRACT
Extrathymic T cell precursors can be detected in many tissues and represent an immediately competent population for rapid T cell reconstitution in the event of immunodeficiencies. Blood T cell progenitors have been detected, but their source in the bone marrow (BM) remains unclear. Prospective purification of BM-resident and circulating progenitors, together with RT-PCR single-cell analysis, was used to evaluate and compare multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). Molecular analysis of circulating progenitors in comparison with BM-resident progenitors revealed that CCR9(+) progenitors are more abundant in the blood than CCR7(+) progenitors. Second, although Flt3(-) CLPs are less common in the BM, they are abundant in the blood and have reduced Cd25(+)-expressing cells and downregulated c-Kit and IL-7Rα intensities. Third, in contrast, stage 3 MPP (MPP3) cells, the unique circulating MPP subset, have upregulated Il7r, Gata3, and Notch1 in comparison with BM-resident counterparts. Evaluation of the populations' respective abilities to generate splenic T cell precursors (Lin(-)Thy1.2(+)CD25(+)IL7Rα(+)) after grafting recipient nude mice revealed that MPP3 cells were the most effective subset (relative to CLPs). Although several lymphoid genes are expressed by MPP3 cells and Flt3(-) CLPs, the latter only give rise to B cells in the spleen, and Notch1 expression level is not modulated in the blood, as for MPP3 cells. We conclude that CLPs have reached the point where they cannot be a Notch1 target, a limiting condition on the path to T cell engagement.
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Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
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Linfócitos B
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Linfócitos T
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Regulação da Expressão Gênica no Desenvolvimento
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Linhagem da Célula
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Células-Tronco Multipotentes
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
França