Multifaceted interactions between adaptive immunity and the central nervous system

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Science  19 Aug 2016:
Vol. 353, Issue 6301, pp. 766-771
DOI: 10.1126/science.aag2638

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  • RE: The Brain and the Lymphatic System
    • Michael Foldi, Professor Professor Emeritus, University of Freiburg, ISL Past President
    • Other Contributors:
      • Etelka Foldi, Director, FoldiKlinik, Hinterzarten, Germany, ISL Past President
      • Marlys Hearst Witte, Professor of Surgery, University of Arizona, ISL Secretary-General and Past President

    We were interested to read your story on “Immune Cells and the Brain” and particularly Kipnis’ article exploring the neglected role of the brain's lymphatic system in immune cell trafficking and immune responses (1). Among “overlooked references” by contemporary researchers who “discovered” the meningeal lymphatic route for immune cells and macromolecules from the CSF into deep cervical lymph nodes (2,3), he cited a 1966 paper (4) coauthored by the first signer below. Now 97, MF challenged evidence even more extensively in subsequent books and papers (5-7) about what had been thought and taught (until almost the current day!) to be the “a-lymphatic” brain. This research demonstrated that the CNS lymphatic system gathers “lymph” from the brain’s perivascular spaces, CSF, and meninges and directly drains through the nasal cavity, orbits, and auditory canal - eventually reaching the cervical lymphatic collectors and lymph nodes. Further, experimental ligation of the cervical lymphatics (in humans, radical cervical lymphadenectomy for cancer or congenital cervical lymphatic hypoplasia) produces a distinctive CNS syndrome of “lymphogenous encephalopathy”, characterized by facial and brain swelling, somnolence and other behavioral disturbances, and characteristic EEG changes. Kipnis’ article attempts to set the historical record straight and also, like the International Society of Lymphology at its founding in 1966, envisions the lymphatic system not simplistically as “lym...

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    Competing Interests: None declared.

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