Ontogeny of naturally occurring CD4⁺ CD25⁺ regulatory T cells.

Laura CODARRI (to May 2007)

Among the mechanisms of control of the immune response allowing effective protection against pathogens, an active role is played by regulatory T (Treg) cells that suppress T cell functions. However, a major challenge in the development of therapeutic strategies using Treg cells is their anergic state that renders difficult any manipulations in vivo or in vitro. Until now, different types of regulatory T cells have been discovered but their inter-relationships remain unknown due to the lack of reliable markers to discriminate them.

We focused our attention on naturally occurring CD4⁺CD25⁺ regulatory T cells that have been shown to derive from the thymus in mice. Similar cells have been found in humans but their origin and differentiation remain unclear.

To address this issue, we have studied the CD4⁺CD25⁺ regulatory T cells in the thymus, cord blood and adult peripheral blood and identified CD4⁺CD25⁺CD45RO^-Foxp3⁺ as the precursors of Treg cells. These precursors are not anergic and have not yet acquired a suppressive function and were induced to differentiate in vitro into functional Tregs with the same surface and molecular phenotype of the typical CD4⁺CD25⁺ regulatory T cells.

The identification of a non-anergic precursor Treg cell population provides an ideal cell target in order to develop intervention strategies that may substantially influence the number of mature suppressive T reg cells and thus their immunoregulatory role.

ANIMATION

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Reference:

Codarri L., Lieby P., Harari A., Correa R., Garcia M., De Smedt M., Plum J. and Pantaleo G. Identification of a CD4⁺CD25⁺ T cell population that may serve as the precursor of Human CD4 regulatory T cells in the thymus and blood. Submitted.

Dernière modification le 29.11.2009 - Impressum - Informations juridiques