Neonatal induction of myelin-specific Th1/Th17 immunity does not result in experimental autoimmune encephalomyelitis and can protect against the disease in adulthood.
The neonatal immune system is believed to be biased towards T helper type 2 (Th2) immunity, but under certain conditions neonates can also develop Th1 immune responses. Neonatal Th2 immunity to myelin antigens is not pathogenic and can prevent induction of experimental autoimmune encephalomyelitis (EAE) in adulthood, but the consequences of neonatally induced Th1 immunity to self-antigens have remained unresolved. Here, we show that neonatal injection of mice with myelin antigens emulsified in complete Freund's adjuvant (CFA) induced vigorous production of IFN-gamma and IL-17, but not IL-5, consistent with myelin-specific Th1/Th17 immunity. Importantly, the myelin-specific Th1/Th17 cells persisted in the mice until adulthood without causing symptoms of EAE. Intraperitoneal, but not subcutaneous injection of neonates with myelin antigens protected against induction of EAE as adults. Intraperitoneally injected neonates showed a substantial decrease of the number and avidity of myelin-reactive Th17 cells, suggesting a decrease in IL-17 producing precursor cells as the mechanism of protection from EAE upon re-injection with myelin antigens as adults. The results could provide a rationale for the presence of autoreactive T cells found in healthy human individuals without autoimmune disease.
Hofstetter
Harald H
HH
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Kovalovsky
Andra
A
Shive
Carey L
CL
Lehmann
Paul V
PV
Forsthuber
Thomas G
TG
D019264:Adoptive Transfer / Q000379:methods; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015704:CD4 Antigens / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D007091:Image Processing, Computer-Assisted; D007263:Infusions, Parenteral / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
D015704:CD4 Antigens; D016207:Cytokines; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151)