International Immunology Advance Access originally published online on November 15, 2005
International Immunology 2006 18(5):627-635; doi:10.1093/intimm/dxh344
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sialylation regulates peripheral tolerance in CD4+ T cells
1 Department of Pathology and Laboratory Medicine, 252 John Morgan Building, 36th & Hamilton Walk, and
2 Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA
3 Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92093, USA
Correspondence to: M. I. Greene; E-mail: greene{at}reo.med.upenn.edu
Decreased binding by the 6C10 auto-antibody serves as a unique marker for CD4+ T cell unresponsiveness after the induction of T cell tolerance in Vß8.1 TCR transgenic mice. We further define the nature of the epitope recognized by the 6C10 antibody to be a subset of Thy-1 bearing incompletely sialylated N-linked glycans, and furthermore, we demonstrate that tolerant CD4+ T cells have an increased degree of cell-surface sialylation. To test the significance of the altered glycosylation state identified by the 6C10 auto-antibody in the tolerant CD4+ T cell population, surface sialic acid was cleaved enzymatically. Treatment of purified peripheral CD4+ T cells with Vibrio cholerae sialidase (VCS) leads to increased 6C10 binding, significantly enhances proliferation in the tolerant CD4+ population and corrects defects in phosphotyrosine signaling observed in the tolerant CD4+ T cell. Furthermore, in vivo administration of VCS enhances proliferation in both tolerant and naive CD4+ T cell subsets. These studies suggest that sialylation of glycoproteins on the surface of the CD4+ T cell contributes to the regulation of T cell responsiveness in the tolerant state.
Keywords: T cell, tolerance, sialylation, superantigen
Transmitting editor: T. Hamaoka
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Kuball, B. Hauptrock, V. Malina, E. Antunes, R.-H. Voss, M. Wolfl, R. Strong, M. Theobald, and P. D. Greenberg Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain J. Exp. Med., February 16, 2009; 206(2): 463 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Woodard-Grice, A. C. McBrayer, J. K. Wakefield, Y. Zhuo, and S. L. Bellis Proteolytic Shedding of ST6Gal-I by BACE1 Regulates the Glycosylation and Function of {alpha}4{beta}1 Integrins J. Biol. Chem., September 26, 2008; 283(39): 26364 - 26373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Hernandez, J. Klein, S. J. Van Dyken, J. D. Marth, and L. G. Baum T-cell activation results in microheterogeneous changes in glycosylation of CD45 Int. Immunol., July 2, 2007; (2007) dxm053v1. [Abstract] [Full Text] [PDF]
|
|