Frontiers in Immunology (Jun 2024)

Sialic acids on T cells are crucial for their maintenance and survival

  • Michael Schmidt,
  • Alexandra T. Linder,
  • Marina Korn,
  • Nick Schellenberg,
  • Sarah J. Meyer,
  • Falk Nimmerjahn,
  • Anja Werner,
  • Markus Abeln,
  • Rita Gerardy-Schahn,
  • Anja K. Münster-Kühnel,
  • Lars Nitschke

DOI
https://doi.org/10.3389/fimmu.2024.1359494
Journal volume & issue
Vol. 15

Abstract

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Sialic acids are found as terminal sugars on glycan structures on cellular surfaces. T cells carry these sialoglycans abundantly, and they are thought to serve multiple functions in cell adhesion, cell migration, and protection from complement attack. We studied the role of sialoglycans on T cells in a mouse model with a T cell-specific deletion of cytidine monophosphate-sialic acid synthase (CMAS), the enzyme that is crucial for the synthesis of sialoglycans. These mice showed a T-cell deficiency in peripheral lymphoid organs. Many T cells with an undeleted Cmas allele were found in the periphery, suggesting that they escaped the Cre-mediated deletion. The remaining peripheral T cells of T cell-specific Cmas KO mice had a memory-like phenotype. Additional depletion of the complement factor C3 could not rescue the phenotype, showing that the T-cell defect was not caused by a host complement activity. Cmas-deficient T cells showed a high level of activated caspase 3, indicating an ongoing apoptosis. In bone marrow chimeric cellular transfer experiments, we observed a strong competitive disadvantage of Cmas-deficient T cells compared to wild-type T cells. These results show that sialoglycans on the surface of T cells are crucial for T-cell survival and maintenance. This function has not been recognized before and is similar to the function of sialoglycans on B cells.

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