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Cutting Edge: Size and Diversity of CD4⁺CD25^high Foxp3⁺ Regulatory T Cell Repertoire in Humans: Evidence for Similarities and Partial Overlapping with CD4⁺CD25^– T Cells¹

Nicolas Fazilleau^2,*, Hervé Bachelez, Marie-Lise Gougeon^* and Manuelle Viguier^2,*

^* Unité de Recherche et d’Expertise Immunité Anti-virale, Biothérapie et Vaccins, Institut National de la Santé et de la Recherche Médicale (INSERM) U668, Institut Pasteur; and INSERM U697, Université Paris 7, Hôpital Saint-Louis. Paris, France

Both differentiation and function of CD4⁺CD25^high naturally arising regulatory T cells (Treg), which play a key role in the control of autoimmunity, are thought to depend on TCR specificity. In the present study, we comparatively measured the TCR repertoire sizes of human peripheral blood Treg and CD4⁺CD25^– T cells by using a methodology based on PCR amplification and sequencing analysis. We show that Treg use a large unrestricted TCR repertoire, the size and diversity of which are closely similar to those of CD4⁺CD25^– T cells, with a mean estimated size of 3.5 x 10⁶ distinct TCR vs 4.7 x 10⁶ distinct TCR for CD4⁺CD25^– T cells. In addition, a 24% overlap between the repertoires of these two CD4⁺ subsets in the periphery is found. These data emphasize the intersection between naturally occurring Treg and effector T cell peripheral repertoires and provide new insights into the ontogeny of Treg in humans.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by fellowships from Ligue contre le Cancer, Association pour la Recherche contre le Cancer, INSERM, Institut Pasteur, Ministère de la Recherche Française, and Pasteur-Weizmann.

² Address correspondence and reprint requests to Dr. Nicolas Fazilleau at the current address: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla CA 92037; E-mail address: nicolas{at}scripps.edu or Dr. Manuelle Viguier, Service Dermatologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France; E-mail address: manuelle.viguier{at}sls.aphp.fr

³ Abbreviations used in this paper: Treg, regulatory T cell; HD, healthy donor; MLE, maximum likelihood estimate.

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