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Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

Item Type:Article
Title:Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE
Creators Name:van Zwam, M. and Huizinga, R. and Melief, M.J. and Wierenga-Wolf, A.F. and van Meurs, M. and Voerman, J.S. and Biber, K.P. and Boddeke, H.W. and Hoepken, U.E. and Meisel, C. and Meisel, A. and Bechmann, I. and Hintzen, R.Q. and 't Hart, B.A. and Amor, S. and Laman, J.D. and Boven, L.A.
Abstract:Drainage of central nervous system (CNS) antigens to the brain-draining cervical lymph nodes (CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis (MS). We demonstrate neuronal antigens within CLN of MS patients. In monkeys and mice with experimental autoimmune encephalomyelitis (EAE) and in mouse models with non-inflammatory CNS damage, the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph nodes. In addition, CNS antigens drained to the spinal-cord-draining lumbar lymph nodes. In human MS CLN, neuronal antigens were present in pro-inflammatory antigen-presenting cells (APC), whereas the majority of myelin-containing cells were anti-inflammatory. This may reflect a different origin of the cells or different drainage mechanisms. Indeed, neuronal antigen-containing cells in human CLN did not express the lymph node homing receptor CCR7, whereas myelin antigen-containing cells in situ and in vitro did. Nevertheless, CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type mice. We conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS damage. Furthermore, the presence of myelin and neuronal antigens in functionally distinct APC populations within MS CLN suggests that differential immune responses can be evoked.
Keywords:Neuroinflammation, Immune Regulation, Autoreactive T Cells, Tolerance, Chemokines, Cytokines, Animals, Mice, Macaca Mulatta
Source:Journal of Molecular Medicine
ISSN:0946-2716
Publisher:Springer
Volume:87
Number:3
Page Range:273-286
Date:March 2009
Official Publication:https://doi.org/10.1007/s00109-008-0421-4
PubMed:View item in PubMed

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