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Joost Smolders1,2, Kirstin M Heutinck3, Nina L Fransen4

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Area of Science:

  • Neuroimmunology
  • Immunology
  • Cell Biology

Background:

  • Tissue-resident memory T cells (TRM cells) are vital for local tissue protection against pathogens.
  • The presence and function of TRM cells in the human brain remain incompletely understood.

Purpose of the Study:

  • To investigate the presence and characteristics of TRM cells within the human brain.
  • To determine the role of TRM cells in brain immunity and their regulation.

Main Methods:

  • Phenotypic and transcription factor analysis of human white matter-derived CD8+ and CD4+ T cells.
  • Assessment of T cell markers associated with tissue residency, differentiation, and immune checkpoints.

Main Results:

  • Human brain CD8+ T cells exhibit TRM cell phenotypes, including CD103 and CD69 expression.
  • CD103 expression on brain CD8+ TRM cells correlates with specific transcription factor profiles, chemokine receptors, and immune checkpoint molecules (PD-1, CTLA-4).
  • Brain CD4+ T cells show TRM-associated markers but lower CD103 expression.

Conclusions:

  • The human brain harbors TRM cells that provide surveillance against neurotropic viruses.
  • Brain TRM cell activity is tightly regulated by immune checkpoint molecules, balancing protection and immune control.