Interaction of astrocytes and T cells in physiological and pathological conditions

Abstract

The central nervous system (CNS) has long been recognized as a site of ‘immune privilege’ because of the existence of the blood brain barrier (BBB) which presumably isolates CNS from the peripheral immunosurveillance. Different from the peripheral organs, CNS is unique in response to all forms of CNS injury and disease which is mainly mediated by resident microglia and astrocyte. There is increasing evidence that immune cells are not only involved in neuroinflammation process but also the maintenance of CNS homeostasis. T cells, an important immune cell population, are involved in the pathogenesis of some neurological diseases by inducing either innate or adaptive immune responses. Astrocytes, which are the most abundant cell type in the CNS, maintain the integrity of BBB and actively participate in the initiation and progression of neurological diseases. Surprisingly, how astrocytes and T cells interact and the consequences of their interaction are not clear. In this review we briefly summarized T cells diversity and astrocyte function. Then, we examined the evidence for the astrocytes and T cells interaction under physiological and pathological conditions including ischemic stroke, multiple sclerosis, viral infection, and Alzheimer’s disease.

Age-Associated Resident Memory CD8 T Cells in the Central Nervous System Are Primed To Potentiate Inflammation after Ischemic Brain Injury

“…For example, astrocyte-secreted CXCL10 promotes the recruitment and entry of lymphocytes into the CNS, and worsens acute spinal cord demyelination in EAE (56, 57). Indeed, there is a growing appreciation for astrocyte-T cell interactions (58–60). The impact of CNS-resident CD8 T cells on astrocyte functions in aged brains remains to be shown.…”

Astrocyte-Derived Pentraxin 3 Supports Blood–Brain Barrier Integrity Under Acute Phase of Stroke

“…Blood-brain barrier (BBB) leakage contributes significantly to the progression of secondary brain injury after ischemic stroke 1 . Although the primary substrate of BBB injury may involve dysfunction in tight junction proteins within the affected endothelium, emerging data now suggest that gliovascular interactions may also be important.…”

Changes in Vascular and Immune Cell Content of an LPS Treated Rat Olfactory Bulb PD Model, Measured by Fluorescence Deconvolution Microscopy

“…While it is now accepted that PD is a results of an inflammatory episode and subsequent microglia activation, increasing loss of functioning dopaminergic neurons [34], synthesis and release of multiple cytokines, accumulation of toxic substances, subcellular organelle dysfunction and increased effects of invading cells, a loss of BBB integrity, vascular endothelium integrity and astrocyte damage, are strongly implicated in a continuing loss of protective abilities [7,[35][36][37][38][39].…”

“…The same can be said for astrocytes, with 'misplacement' of the cells in PD and Alzheimer's disease and their release of deadly molecules [39]. Thus, protective cells can become harmful during inflammatory episodes and, coupled with an influx of immune cells, causes disruption of the BBB which is exacerbated by usually beneficial astrocytes that are mechanistically altered and interact with invading cells [37][38][39][40]. Indeed, our previous research has shown cuffs of T-cells around vessels after endotoxin treatment, as well as ubiquitin and TNFα in vascular endothelial cells, suggesting that perivascular disruption occurs and that cells respond in both self-preservation and destructive manners [5,43].…”