Cognate microglia–T cell interactions shape the functional regulatory T cell pool in experimental autoimmune encephalomyelitis pathology

Microglia, the parenchymal brain macrophages of the central nervous system, have emerged as critical players in brain development and homeostasis. The immune functions of these cells, however, remain less well defined. We investigated contributions of microglia in a relapsing–remitting multiple sclerosis paradigm, experimental autoimmune encephalitis in C57BL/6 x SJL F₁ mice. Fate mapping-assisted translatome profiling during the relapsing–remitting disease course revealed the potential of microglia to interact with T cells through antigen presentation, costimulation and coinhibition. Abundant microglia–T cell aggregates, as observed by histology and flow cytometry, supported the idea of functional interactions of microglia and T cells during remission, with a bias towards regulatory T cells. Finally, microglia-restricted interferon-γ receptor and major histocompatibility complex mutagenesis significantly affected the functionality of the regulatory T cell compartment in the diseased central nervous system and remission. Collectively, our data establish critical non-redundant cognate and cytokine-mediated interactions of microglia with CD4⁺ T cells during autoimmune neuroinflammation.