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Cellular immune surveillance of central nervous system bypasses blood–brain barrier and blood–cerebrospinal–fluid barrier: Revealed with the N ew M arburg cerebrospinal–fluid model in healthy humans
Author(s) -
Kleine Tilmann O.
Publication year - 2015
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.22589
Subject(s) - circumventricular organs , choroid plexus , cerebrospinal fluid , pathology , area postrema , subfornical organ , ependyma , ependymal cell , medicine , biology , central nervous system , angiotensin ii , immunohistochemistry , blood pressure
In healthy human brain/spinal cord, blood capillaries and venules are locked differently with junctions and basement membrane (blood–brain barrier, blood–venule barrier). In choroid plexus, epithelial tight junctions and basement membrane lock blood‐cerebrospinal‐fluid (CSF) barrier. Lymphocytic cell data, quantified with multicolour flow‐cytometry or immuno‐cytochemical methods in sample pairs of lumbar CSF, ventrictricular CSF and peripheral venous blood, are taken from references; similarly, data of thoracic duct chyle and blood sample pairs. Through three circumventricular organs (median eminence, organum vasculosum lamina terminalis, area postrema), 15–30 μl blood are pressed by blood pressure through fenestrated capillaries, matrix/basement membrane spaces and ependyma cell lacks into ventricular/suboccipital CSF to generate CD3 + , CD4 + , CD8 + , CD3 + HLA‐DR + , CD16 + 56 + 3 – NK, CD19 + 3 – B subsets; some B, few NK cells adhere in circumventricular organs. Into lumbar CSF, 10–15 μl thoracic chyle with five lymphocyte subsets (without CD3 + HLA‐DR + cells) reflux, when CSF drains out with to‐and‐fro movements of chyle/CSF along nerve roots. Lymphocytes in lumbar CSF represent a mixture of blood and lymph lymphocytic cells with similar HLA‐DR + CD3 + cell counts in ventricular and lumbar CSF, higher CD3 + , CD4 + , CD8 + subsets in lumbar CSF, and few NK and B cells due to absorption in circumventricular organs. The Marburg CSF Model reflects origin and turnover of lymphatic cells in CSF realistically; the model differs from ligand‐multistep processes of activated lymphocytes through blood–brain‐, blood–venule‐, and blood–CSF‐barriers; because transfer of inactivated native lymphocytes through the barriers is not found with healthy humans, although described so in literature. © 2015 International Society for Advancement of Cytometry