Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE.
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.
van Zwam
Marloes
M
Department of Immunology, Erasmus MC, CA, Rotterdam, The Netherlands.
Huizinga
Ruth
R
Melief
Marie-José
MJ
Wierenga-Wolf
Annet F
AF
van Meurs
Marjan
M
Voerman
Jane S
JS
Biber
Knut P H
KP
Boddeke
Hendrikus W G M
HW
Höpken
Uta E
UE
Meisel
Christian
C
Meisel
Andreas
A
Bechmann
Ingo
I
Hintzen
Rogier Q
RQ
't Hart
Bert A
BA
Amor
Sandra
S
Laman
Jon D
JD
Boven
Leonie A
LA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology; D000941:Antigens / Q000276:immunology*; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002144:Callithrix; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000941:Antigens; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7