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Sialylation regulates peripheral tolerance in CD4+ T cells.
Patrick J Brennan1, Sandra J Saouaf, Steve Van Dyken
1Department of Pathology and Laboratory Medicine, 252 John Morgan Building, 36th & Hamilton Walk, Philadelphia, PA 19104-6082, USA.
International Immunology
|November 18, 2005
Summary
Altered T cell glycosylation, specifically increased sialylation, marks T cell tolerance. Enzymatic removal of sialic acid restores T cell responsiveness and signaling, suggesting a role for sialylation in regulating T cell function.
Area of Science:
- Immunology
- Glycobiology
- Cellular Biology
Background:
- T cell tolerance is crucial for preventing autoimmunity.
- The 6C10 auto-antibody identifies a marker for unresponsive CD4+ T cells.
- Altered cell-surface glycosylation is observed in tolerant T cells.
Purpose of the Study:
- To investigate the role of altered glycosylation in T cell tolerance.
- To define the epitope recognized by the 6C10 auto-antibody.
- To determine if modulating sialylation can restore T cell responsiveness.
Main Methods:
- Characterization of the 6C10 antibody epitope on T cells.
- Enzymatic cleavage of cell-surface sialic acid using Vibrio cholerae sialidase (VCS).
- Assessment of T cell proliferation and phosphotyrosine signaling post-VCS treatment.
Main Results:
- The 6C10 epitope is associated with incompletely sialylated N-linked glycans on Thy-1.
- Tolerant CD4+ T cells exhibit increased cell-surface sialylation.
- VCS treatment of tolerant T cells enhanced proliferation and corrected signaling defects.
- In vivo VCS administration boosted proliferation in both tolerant and naive CD4+ T cells.
Conclusions:
- Increased T cell sialylation is a marker of T cell unresponsiveness in tolerance.
- Modulating cell-surface sialylation can restore T cell responsiveness.
- Glycoprotein sialylation plays a regulatory role in T cell function during tolerance.