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CD101 Surface Expression Discriminates Potency Among Murine FoxP3⁺ Regulatory T Cells¹

Irina Fernandez^*, Robert Zeiser, Holger Karsunky^*, Neeraja Kambham^*, Andreas Beilhack, Kalle Soderstrom^*, Robert S. Negrin and Edgar Engleman^2,*

^* Department of Pathology, and Division of Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305

CD4⁺CD25⁺FoxP3⁺ regulatory T cells (Treg) have been shown to be protective in animal models of autoimmunity and acute graft-vs-host disease. However, owing to the functional heterogeneity among CD4⁺CD25⁺ T cells, surface markers expressed selectively on functionally active Treg would be useful for purposes of identifying and isolating such cells. We generated a rabbit mAb against murine CD101, a transmembrane glycoprotein involved in T cell activation. Among freshly isolated T cells, CD101 was detected on 25–30% of CD4⁺CD25⁺ Treg and 20% of conventional memory T cells. CD101^high Treg displayed greater in vitro suppression of alloantigen-driven T cell proliferation as compared with CD101^low Treg. In a model of graft-vs-host disease induced by allogeneic bone marrow transplantation in vivo bioluminescence imaging demonstrated reduced expansion of donor-derived luciferase-labeled conventional T cells in mice treated with CD101^high Treg, compared with CD101^low Treg. Moreover, treatment with CD101^high Treg resulted in improved survival, reduced proinflammatory cytokine levels and reduced end organ damage. Among the CD101^high Treg all of the in vivo suppressor activity was contained within the CD62L^high subpopulation. We conclude that CD101 expression distinguishes murine Treg with potent suppressor activity.

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 study was supported by Grants RO1 CA0800065, P01 HL075462, and RO1 AR051748 from the National Institutes of Health and by Dr. Mildred-Scheel-Stiftung, Germany (to R.Z.).

² Address correspondence and reprint requests to Dr. Edgar Engleman, Department of Pathology, Stanford Blood Center, 3373 Hillview Avenue, Palo Alto, CA 94304. E-mail address: edengleman{at}stanford.edu

³ Abbreviations used in this paper: Treg, CD4⁺CD25⁺ regulatory T cell; GITR, glucocorticoid-induced TNFR; DC, dendritic cell; GVHD, graft-vs-host disease; CD62L, CD62 ligand; BMT, bone marrow transplantation.

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