Role of the cervical lymphatics in the Th2-type hierarchy of CNS immune regulation

CNS immune regulation is intimately dependent on the dynamics of cerebral extracellular fluid circulation. Animal models indicate that following the introduction of antigen into the CNS, normal circulation of interstitial and cerebrospinal fluids provides the opportunity for (a) delivery of CNS-deri...

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Bibliographic Details
Published in:Journal of Neuroimmunology 1999-11, Vol.101 (2), p.111-127
Main Authors: Harling-Berg, Christine J, Park, Joel T, Knopf, Paul M
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Antibody Formation
B lymphoblast migration
Brain - immunology
Cerebral interstitial fluid
Cerebrospinal fluid
Cerebrospinal Fluid - physiology
Cervical lymph nodes
CNS antibody production
extracellular fluid
Extracellular Space - physiology
Humans
Hypersensitivity, Delayed
Immune privilege
interstitial fluid
Lymph Nodes - physiology
Lymphocyte Activation
Neck
T-Lymphocytes, Cytotoxic - immunology
Th2 Cells - immunology
Th2 lymphocytes
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Summary:CNS immune regulation is intimately dependent on the dynamics of cerebral extracellular fluid circulation. Animal models indicate that following the introduction of antigen into the CNS, normal circulation of interstitial and cerebrospinal fluids provides the opportunity for (a) delivery of CNS-derived antigen to lymphoid organs, as well as, (b) retention of immunologically significant amounts of antigen within the CNS. Thus, even in the absence of disease, CNS-derived antigen can induce antigen-specific activation of naive lymphocytes in lymphoid organs and specific reactivation of lymphoblasts that have migrated into the CNS. The initial peripheral immune response to CNS-derived antigen is induced in cervical lymph nodes and is characterized by a strong antibody response, no delayed-type hypersensitivity, and only priming for cytototoxic T-cell responses. This Th-2 type hierarchy of immune regulation is reinforced within the antigen-stimulated CNS where specific B lymphoblasts are permitted to develop their effector function but cell-mediated immunity is inhibited. Developing a paradigm for CNS immune regulation is important in understanding how CNS disorders in humans are induced, perpetuated, and may be manipulated.
ISSN:0165-5728
1872-8421
DOI:10.1016/S0165-5728(99)00130-7