When encephalitogenic T cells collaborate with microglia in multiple sclerosis

Immune cells mediate critical inflammatory and neurodegenerative processes in the CNS in individuals with multiple sclerosis (MS). In MS, activated microglia, border-associated macrophages and monocyte-derived macrophages in the CNS can encounter T cells that have infiltrated the brain parenchyma from the circulation. Although microglia and T cells both contribute to normal CNS development and homeostasis, evidence suggests that the meeting of activated microglia and macrophages with encephalitogenic T cells exacerbates their capacity to inflict injury. This crosstalk involves many cell-surface molecules, cytokines and neurotoxic factors. In this Review, we summarize the mechanisms and consequences of T cell–microglia interactions as identified with in vitro experiments and animal models, and discuss the challenges that arise when translating this preclinical knowledge to MS in humans. We also consider therapeutic approaches to MS of which the mechanisms involve prevention or modulation of T cell and microglia responses and their interactions. In this Review, Dong and Yong summarize the mechanisms and consequences of T cell–microglia interactions in multiple sclerosis, discuss therapeutic approaches that affect these interactions and consider the challenges of translating preclinical knowledge in this area to humans. Key points Microglia and T cells help to maintain homeostasis in the CNS. Activated microglia and macrophages in the CNS interact with T cells via cell-to-cell contact and cytokine-mediated communication to promote neuroinflammation in an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Monocytes and monocyte-derived cells add heterogeneity to the CNS macrophage population in EAE and MS and could also interact with T cells to regulate disease pathology. Several challenges are involved in translating T cell–microglia interactions identified in vitro or in animal models to MS, so these findings should be considered carefully when generalizing to the human disease. The mechanisms of existing and potential MS therapeutics involve interference with the interactions and functions of T cells and microglia, but the contribution of these effects is difficult to confirm.