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CNS immune privilege: hiding in plain sight.

Monica J Carson¹, Jonathan M Doose, Benoit Melchior

¹Division of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA. monica.carson@ucr.edu

Immunological Reviews

|September 16, 2006

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The central nervous system (CNS) is not isolated but actively interacts with the immune system. Understanding this immune privilege is key for developing new therapies for CNS autoimmune and neurodegenerative diseases.

Area of Science:

Neuroimmunology
Central Nervous System (CNS) Research
Immune Privilege

Background:

Historically, CNS immune privilege was attributed to the blood-brain barrier (BBB), lack of lymphatics, and microglia incompetence.
This view presumed CNS autoimmunity and neurodegeneration result from immune cell encounters with CNS antigens.

Purpose of the Study:

To re-evaluate the concept of CNS immune privilege based on recent findings.
To explore the implications of a dynamic CNS-immune interaction for neuroinflammation and neurodegeneration.

Main Methods:

Review and synthesis of recent experimental data on CNS-immune interactions.
Analysis of the roles of the BBB, lymphatics, microglia, neurons, and glia in immune regulation within the CNS.

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Main Results:

The CNS is not isolated; peripheral immune cells can cross the intact BBB.
CNS neurons and glia actively regulate immune responses, and microglia are immunocompetent.
Microglia exhibit unique abilities to direct neuroprotective lymphocyte responses.

Conclusions:

CNS immune privilege is a dynamic regulatory process, not mere isolation.
Dysfunction in CNS autoimmune diseases (e.g., multiple sclerosis) may stem from neuronal/glial issues as much as immune problems.
Neuronal/glial dysfunction in neurodegenerative diseases (e.g., Alzheimer's) impacts lymphocyte regulation, affecting immune-based therapies.