title: Cellular immune surveillance of central nervous system bypasses blood-brain barrier and blood-cerebrospinal-fluid barrier: revealed with the New Marburg cerebrospinal-fluid model in healthy humans.
abstract: 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.
authors: Department of Laboratory Medicine and Molecular Diagnostics of the University Hospital Marburg. Dependance: Cerebrospinal-Fluid References Labor, Baldingerstraße, 35043, Marburg, Germany.
authors: Tilmann O
authors: TO
authors: Kleine
mesh_terms: D001812:Blood-Brain Barrier / Q000166:cytology* / Q000276:immunology*; D001921:Brain / Q000166:cytology / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008959:Models, Neurological
keywords: B cells; NK cells; blood-CSF barrier; blood-brain barrier; blood-venule barrier; blood-venule-leptomeninges barrier; cerebrospinal-fluid (CSF); flow-cytometry-immunophenotyping; human lymphocytes; thoracic chyle lymphocytes