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Trafficking of antigen-presenting cells into the CNS is essential for lymphocyte reactivation within the CNS compartment. Although perivascular dendritic cells found in inflammatory lesions are reported to polarize naive CD4⁺ T lymphocytes into interleukin-17-secreting-cells, the origin of those antigen-presenting cells remains controversial. We demonstrate that a subset of CD14⁺ monocytes migrate across the inflamed human blood–brain barrier (BBB) and differentiate into CD83⁺CD209⁺ dendritic cells under the influence of BBB-secreted transforming growth factor-β and granulocyte-macrophage colony-stimulating factor. We also demonstrate that these dendritic cells secrete interleukin-12p70, transforming growth factor-β and interleukin-6 and promote the proliferation and expansion of distinct populations of interferon-γ-secreting Th1 and interleukin-17-secreting Th17 CD4⁺ T lymphocytes. We further …