Conventional DCs sample and present myelin antigens in the healthy CNS and allow parenchymal T cell entry to initiate neuroinflammation

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Science Immunology  25 Jan 2019:
Vol. 4, Issue 31, eaau8380
DOI: 10.1126/sciimmunol.aau8380

Licensing myelin-reactive T cells

Multiple distinct populations of potential antigen-presenting cells (APCs) are interspersed among the different anatomical components of the brain, including microglia, B lymphocytes, macrophages, and dendritic cells (DCs). Mundt et al. investigated which steady-state APC types are responsible for displaying peptide fragments of myelin proteins to pathogenic CD4+ T cells with the capacity to initiate neuroinflammatory disorders such as human multiple sclerosis. Adoptive transfer of myelin-reactive CD4+ T cells to mice with conditional deletion of MHC class II molecules in specific brain APC subsets identified conventional DCs as the essential APCs enabling initiation of T cell–mediated immunopathology. The results of this study will assist in the precision targeting of immunotherapies aimed at restraining rogue T cells responsible for human neuroinflammatory diseases.

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