Myelin-basic protein-reactive specific CD4+ and CD8+ NK lymphocytes induce morphological changes in neuronal cell bodies and myelin sheaths: implications for multiple sclerosis.
BACKGROUND
Multiple sclerosis (MS) is a chronic disease characterized by loss of myelin. However, data indicate that autoimmune cells could directly impair neuronal cell bodies and myelin sheath is lacking. The aim of the present study was to determine morphological evidence of the direct impairment of neurons by autoreactive lymphocytes and to further identify the subtypes of these lymphocytes.


METHODS
Lymphocytes activated by myelin basic protein (MBP) 83-99 and neurons of human brain were co-cultured for 24 h.


RESULTS
Observations through scanning electron microscope showed that MBP-specific lymphocytes (CD4+, CD8+ cells, and NK cells) aggregated in the vicinity of the neuronal cell bodies and the myelin sheaths and attacked them directly, resulting in the degeneration of both neurons.


CONCLUSIONS
Our studies provide morphological evidences of the direct impairment of neuronal cell bodies and myelin sheaths by MBP-specific lymphocytes. Our studies also suggest that MBP-specific CD4+, CD8+, and NK cells might be involved in this process. These processes may play a role in the direct impairment of neurons and myelin sheaths in early stages of MS and provide evidences for the application of immunosuppressant therapy of MS.
Zhang
Quan-yu
QY
Department of Stomatology, Tangdu Hospital, Xi'an, China.
Huang
Jing-hui
JH
Li
Hong-zeng
HZ
Guo
Hai-tao
HT
Zhong
Yan-qing
YQ
Wang
Yue-min
YM
Pei
Jian-ming
JM
D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D004676:Myelin Basic Protein / Q000032:analysis / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology* / Q000648:ultrastructure; D009474:Neurons / Q000276:immunology* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C104448:myelin basic protein 83-99