Journal of Neuroimmune Pharmacology

, Volume 8, Issue 4, pp 840–856 | Cite as

Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes

INVITED REVIEW

Abstract

Despite the absence of conventional lymphatics, there is efficient drainage of both cerebrospinal fluid (CSF) and interstitial fluid (ISF) from the CNS to regional lymph nodes. CSF drains from the subarachnoid space by channels that pass through the cribriform plate of the ethmoid bone to the nasal mucosa and cervical lymph nodes in animals and in humans; antigen presenting cells (APC) migrate along this pathway to lymph nodes. ISF and solutes drain from the brain parenchyma to cervical lymph nodes by a separate route along 100–150 nm wide basement membranes in the walls of cerebral capillaries and arteries. This pathway is too narrow for the migration of APC so it is unlikely that APC traffic directly from brain parenchyma to lymph nodes by this route. We present a model for the pivotal involvement of regional lymph nodes in immunological reactions of the CNS. The role of regional lymph nodes in immune reactions of the CNS in virus infections, the remote influence of the gut microbiota, multiple sclerosis and stroke are discussed. Evidence is presented for the role of cervical lymph nodes in the induction of tolerance and its influence on neuroimmunological reactions. We look to the future by examining how nanoparticle technology will enhance our understanding of CNS-lymph node connections and by reviewing the implications of lymphatic drainage of the brain for diagnosis and therapy of diseases of the CNS ranging from neuroimmunological disorders to dementias. Finally, we review the challenges and opportunities for progress in CNS-lymph node interactions and their involvement in disease processes.

Keywords

Antigen presenting cells CSF Interstitial fluid Nasal lymphatics Cervical lymph nodes Dendritic cells Perivascular drainage Immune privilege Multiple sclerosis Regulatory T and B cells Tolerance Stroke 

Abbreviations

APC

Antigen presenting cell

CLN

Cervical lymph nodes

CNS

Central nervous system

CSF

Cerebrospinal fluid

DC

Dendritic cells

EAE

Experimental autoimmune/allergic encephalomyelitis

GFP

Green fluorescent protein

ISF

Interstitial fluid

MBP

Myelin basic protein

MOG

Myelin oligodendrocyte glycoprotein

MRI

Magnetic resonance imaging

MS

Multiple sclerosis

OVA

Ovalbumin

PLP

Proteolipid protein

Treg

Regulatory T cells

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Immunology, room NB-1148a Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands
  2. 2.Clinical Neurosciences, Faculty of MedicineSouthampton UniversitySouthamptonUK

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