FoxP3 is a key transcription factor for the development and function of natural CD4+ regulatory T cells (Treg cells).

The authors show that human FoxP3+CD4+ T cells were composed of three phenotypically and functionally distinct subpopulations: CD45RA+FoxP3lo resting Treg cells (rTreg cells) and CD45RA_FoxP3hi activated Treg cells (aTreg cells), both of which were suppressive in vitro, and cytokine-secreting CD45RA_FoxP3lo nonsuppressive T cells. The proportion of the three subpopulations differed between cord blood, aged individuals, andpatients with immunologicaldiseases. Terminally differentiated aTreg cells rapidly died whereas rTreg cells proliferated and onverted into aTreg cells in vitro and in vivo. This was shown by the transfer of rTreg cells into NOD-scid-common g-chain-deficient mice and by TCR sequence-based T cell clonotype tracing in peripheral blood in a normal individual.

Taken together, the dissection of FoxP3+ cells into subsets enables one to analyze Treg cell differentiation dynamics and interactions in normal and disease states, and to control immune responses through manipulating particular FoxP3+ subpopulations.

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Contact:

Shimon Sakaguchi
Laboratory of Experimental Immunology,
WPI Immunology Frontier Research Center, Osaka University

Tel: +81-75-751-3888, Fax: +81-75-751-3820
shimon@frontier.kyoto-u.ac.jp