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Cosmc is required for T cell persistence in the periphery.

Christopher E Cutler1,2, Mark B Jones1,3, Alicia A Cutler4

  • 1Department of Surgery, Beth Israel Deaconess Medical Center, CLS 11087, 3 Blackfan Circle, Boston, MA, USA.

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Extended O-glycosylation is crucial for T cell survival and function. Mice lacking this process show a severe reduction in peripheral T cells, highlighting its importance in adaptive immunity.

Keywords:
CosmcO-GlycosylationO-glycansT cells

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Area of Science:

  • Immunology
  • Glycobiology
  • Cell Biology

Background:

  • T lymphocytes are vital for adaptive immunity.
  • O-glycosylation dynamically regulates T cell functions.
  • The specific role of O-glycans in T cell maturation is largely unknown.

Purpose of the Study:

  • To investigate the direct role of extended O-glycosylation in T cell maturation and peripheral maintenance.
  • To understand the impact of lacking O-glycans on T cell populations.

Main Methods:

  • Generated T cell conditional Cosmc knockout (TCKO) mice lacking extended O-glycans.
  • Utilized Cre-mediated recombination to specifically target the Cosmc gene in T cells.
  • Analyzed T cell populations in spleen and lymph nodes of TCKO and wild-type (WT) mice.

Main Results:

  • Cosmc deficiency led to near-complete elimination of T cells, reducing total T cell counts to 20% of WT.
  • TCKO thymocytes completed maturation but failed to populate secondary lymphoid organs.
  • Adoptive transfer experiments confirmed impaired peripheral T cell establishment.

Conclusions:

  • Extended O-glycosylation is essential for the establishment and maintenance of peripheral T cell populations.
  • Loss of Cosmc severely impacts T cell persistence and secondary lymphoid organ colonization.
  • This study underscores the critical role of O-glycans in adaptive immune cell homeostasis.