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The Journal of Immunology, 2003, 171: 1691-1696.
Copyright © 2003 by The American Association of Immunologists

Differential Localization and Function of ADP-Ribosylation Factor-6 in Anergic Human T Cells: A Potential Marker for Their Identification1

Dimitrios Tzachanis, Leonard J. Appleman, Andre A. F. L. van Puijenbroek, Alla Berezovskaya, Lee M. Nadler and Vassiliki A. Boussiotis2

Department of Adult Oncology, Dana-Farber Cancer Institute, Division of Medical Oncology, Brigham and Women’s Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115

Anergy is a state of immunologic tolerance in which T cells are viable but incapable of responding to antigenic stimulation. Recent data indicate that anergic cells have a distinct gene expression program that determines their unique function. In this study we show that anergic human T cells selectively express the small GTPase ADP-ribosylation factor-6 (ARF6), which is involved in membrane traffic and regulation of the cortical actin cytoskeleton. ARF6 was expressed in the GTP-bound form that localizes at the plasma membrane, resulting in a distinct morphologic appearance of anergic cells. Forced expression of ARF6-GTP in Jurkat T cells prevented TCR-mediated reorganization of cortical actin, extracellular signal-regulated kinase1/2 activation, and IL-2 transcription. Forced expression of ARF6-GTP in primary human T cells inhibited extracellular signal-regulated kinase1/2 activation and proliferative responses. Importantly, T cells with the distribution pattern of ARF6-GTP were detected in peripheral blood, suggesting that anergic T cells may constitutively exist in vivo.


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