Abstract
While the central nervous system (CNS) was once thought to be immune privileged, more recent data support that certain areas of the healthy CNS are routinely patrolled by immune cells. Further, antigen drainage is another means by which the adaptive arm of the immune system can gain information about the health of the CNS. Altogether these ensure that the CNS is not beyond the scope of immune protection against viruses and tumors. However, immune surveillance in the CNS has to be tightly regulated, as CNS autoimmune disease and inflammation may arise from increased immune cell infiltration. In this review we discuss the concept and implications of CNS immune surveillance and introduce the CNS antigen-presenting cells (APCs) that potentially regulate neuroinflammation and autoimmunity. We also discuss novel animal models in which CNS disease initiation and the role of APCs in disease regulation can be tested.
Highlights
The immune system has evolved to help the body fight foreign pathogens and harmful self-intruders, such as tumors
We previously reported a titration effect, in which the number of antigen-pulsed dendritic cells (DCs) injected into the brain positively correlated with their accumulation in the cervical lymph nodes (CLNs), as well as with the numbers of activated antigenspecific T cells recruited to the brain [26]
While astrocytes engineered to express viral neoantigen may activate effector CD8+ T cells in vivo and initiate disease [92], true cross-presentation of viral or myelin antigens by astrocytes in vivo has never been tested. Given their poor ability to phagocytose myelin antigen compared to microglia [93], it seems unlikely that they have any significant contribution in the presentation of self-antigen to T cells recruited to the central nervous system (CNS) during neuroinflammation
Summary
The immune system has evolved to help the body fight foreign pathogens and harmful self-intruders, such as tumors. Immunity requires continual surveillance of the body by immune cells, primarily tissue-resident macrophages and dendritic cells (DCs), which initiate inflammatory responses that result in the recruitment of T cells and other leukocytes to the site of infection or damage This process is highly restricted in the healthy central nervous system (CNS) due to several regulatory factors that preclude the infiltration of activated T cells from the blood into the CNS parenchyma, contributing to the immune privileged status of the CNS. One idea is that immune cells, DCs, which accumulate in the CNS under inflammatory conditions may pick up and deliver myelin antigens to lymph nodes for the priming of adaptive immune responses This process could lead to the initiation or exacerbation of CNS autoimmune disease. We will further discuss current models of CNS autoimmune disease initiation, and consider the potential contribution of damage-associated molecules to the exacerbation of CNS autoimmunity
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