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| Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses. Guillaume Darrasse-Jèze, Gilles Marodon, Gilles Marodon, Martin Catala, David Klatzmann BLOOD 2005; 105(12):4715-4721 ICID: 433034 |
| Article type: Original article |
| IC™ Value: 19.78 |
| Little is known about the ontogeny of naturally occurring CD4(+)CD25(+)regulatory/suppressor T cells that play a major role in maintaining self-tolerance in mice and humans.In rodents, thymectomy on day 3 of life leads to multiple organ-specific autoimmune diseases that canbe prevented by adoptive transfer of regulatory T cells, suggesting their neonatal development. We investigatedregulatory T-cell ontogeny in 11 human fetuses. Together with the first mature T cells, thymic CD4(+)CD25(+)cells were detected as early as 13 weeks of gestation. Thymic CD25(+) cells appeared to be positivelyselected at the CD4(+)CD8(+)CD3(hi) differentiation stage, as assessed by CD1a and CD69 expression. Theproportion of thymic CD4(+)CD25(+) cells appeared quite stable with age, around 6% to 7%, similar tothe proportion observed in infant thymi. Extrathymic CD4(+)CD25(+) T cells could hardly be detected at13 weeks of gestation but were present from week 14 onwards. As adult regulatory T cells, purified CD4(+)CD25(+)fetal cells were anergic and suppressed T-cell proliferative responses; they expressed intracellularcytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and Foxp3 mRNA. Altogether, our results indicatethat the generation of regulatory/suppressor T cells is consubstantial to the generation of a functionaland self-tolerant immune system. |
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ICID 433034 PMID 15731180 - click here to show this article in PubMed database |
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