Sialylation regulates peripheral tolerance in CD4+ T cells.
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 Vbeta8.1 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.
Brennan
Patrick J
PJ
Department of Pathology and Laboratory Medicine, 252 John Morgan Building, 36th & Hamilton Walk, Philadelphia, PA 19104-6082, USA.
Saouaf
Sandra J
SJ
Van Dyken
Steve
S
Marth
Jamey D
JD
Li
Bin
B
Bhandoola
Avinash
A
Greene
Mark I
MI
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000502:physiology*; D047468:Immunoprecipitation; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009439:Neuraminidase / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D019000:Phosphotyrosine / Q000276:immunology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000276:immunology / Q000378:metabolism; D014734:Vibrio cholerae / Q000201:enzymology
D001323:Autoantibodies; D018800:Thy-1 Antigens; D019000:Phosphotyrosine; D009439:Neuraminidase