International Immunology Advance Access published online on November 15, 2005
International Immunology, doi:10.1093/intimm/dxh344
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1 Department of Pathology and Laboratory Medicine, 252 John Morgan Building, 36th & Hamilton Walk, Philadelphia, PA 19104-6082, USA; Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA
* To whom correspondence should be addressed. 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 V
Received August 18, 2005
Accepted September 30, 2005
Article
Sialylation regulates peripheral tolerance in CD4+ T cells
Patrick J. Brennan 1,
Sandra J. Saouaf 2,
Steve Van Dyken 3,
Jamey D. Marth 3,
Bin Li 2,
Avinash Bhandoola 2,
and
Mark I. Greene 1 *
2 Department of Pathology and Laboratory Medicine, 252 John Morgan Building, 36th & Hamilton Walk, 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
Mark I. Greene, E-mail: greene{at}reo.med.upenn.edu
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Abstract
8.1 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.![]()
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