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September 10, 2026Nature NeuroscienceOpen Access

Intestinal infections establish antigen-specific, long-lived memory CD4+ T cells in the brain and meninges

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Authors

AFAaron FlemingKNKaren NeishRBRafael Di Marco Barros

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Overview

Experimental study reveals gut infections establish long-lived memory CD4+ T cells in the meninges, highlighting a direct immune bridge protecting central nervous system borders.

Key Points

  • Investigate whether gastrointestinal infections establish long-term, pathogen-specific CD4+ T cell immunological memory within the meningeal borders of the central nervous system.
  • Challenged animal models with intracellular bacteria, extracellular bacteria, or parasites via the gastrointestinal tract.
  • Tracked the trafficking and polarization of gut-activated CD4+ T cells to the dura mater, dural venous sinuses, and brain tissue.
  • Evaluated the role of the CXCR6–CXCL16 chemokine axis in central nervous system homing and measured memory recall responses following systemic rechallenge.
  • Intestinal infections reprogrammed dural CD4+ T cell profiles into distinct TH1, TH17, or TH2 polarization states mirroring the specific enteric pathogen.
  • Gut-primed CD4+ T cells localized to dural lymphoid aggregates and venous sinuses via CXCR6–CXCL16 signaling to form permanent resident memory pools.
  • Dural memory cells demonstrated rapid recall capacity upon intravenous antigen re-exposure, proliferating extensively and secreting effector cytokines.

Cite This Study

Fleming et al. (2026) studied this question.

synapsesocial.com/papers/6aa27b3558559d80afc74582https://doi.org/10.1038/s41593-026-02428-4
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