|
|
||||||||
Department of Adult Oncology, Dana-Farber Cancer Institute, Division of Medical Oncology, Brigham and Womens 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.
Related articles in The JI:
This article has been cited by other articles:
![]() |
M. Dominguez-Villar, A. Munoz-Suano, B. Anaya-Baz, S. Aguilar, J. P. Novalbos, J. A. Giron, M. Rodriguez-Iglesias, and F. Garcia-Cozar Hepatitis C virus core protein up-regulates anergy-related genes and a new set of genes, which affects T cell homeostasis J. Leukoc. Biol., November 1, 2007; 82(5): 1301 - 1310. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. I. Mead, Y. Zheng, C. N. Manzotti, L. C. A. Perry, M. K. P. Liu, F. Burke, D. J. Powner, M. J. O. Wakelam, and D. M. Sansom Exocytosis of CTLA-4 Is Dependent on Phospholipase D and ADP Ribosylation Factor-1 and Stimulated during Activation of Regulatory T Cells J. Immunol., April 15, 2005; 174(8): 4803 - 4811. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |