Autoantigen-pulsed dendritic cells induce tolerance to experimental allergic encephalomyelitis (EAE) in Lewis rats.
Dendritic cells (DC) can modulate the nature of immune responses in a stimulatory or tolerogenic fashion. Great attention has been given to the induction of immunity to tumour and infection. In this study, bone marrow-derived DC from healthy Lewis rats were pulsed in vitro with encephalitogenic myelin basic protein peptide 68-86 (MBP 68-86), and injected subcutaneously (1 x 106/rat) into normal Lewis rats. Upon observation of the rats pretreated in this way for 4 weeks, when no clinical signs of EAE occurred, these rats were immunized with MBP 68-86 and Freund's complete adjuvant. The pretreated rats failed to develop clinical EAE. This tolerance was associated with augmented proliferative responses, interferon-gamma secretion, inducible nitric oxide synthase (iNOS) expression and NO production. The frequency of apoptotic cells was increased in the rats receiving MBP 68-86-pulsed DC compared with unpulsed control DC. Few infiltrating inflammatory cells were observed in spinal cord sections from rats that had received MBP 68-86-pulsed DC. The data are compatible with the interpretation that MBP 68-86-pulsed DC induce tolerance to EAE possibly through up-regulation of iNOS expression and NO production, which mediate cell apoptosis, thereby reducing infiltration of inflammatory cells within the central nervous system.
Huang
Y M
YM
Experimental Neurology and Neuroimmunology Units, Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Yang
J S
JS
Xu
L Y
LY
Link
H
H
Xiao
B G
BG
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002455:Cell Division; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000276:immunology*; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D015870:Gene Expression; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D008264:Macrophages / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010446:Peptide Fragments / Q000276:immunology*; D012333:RNA, Messenger; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000166:cytology; D013154:Spleen / Q000166:cytology
D001324:Autoantigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; C110235:myelin basic protein 68-86; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat