Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen.
The cytokine IL-21 is closely related to IL-2 and IL-15, a cytokine family that uses the common gamma-chain for signaling. IL-21 is expressed by activated CD4(+) T cells. We examined the role of IL-21 in the autoimmune disease experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. IL-21 administration before induction of EAE with a neuroantigen, myelin oligodendrocyte glycoprotein peptide 35-55, and adjuvant enhanced the inflammatory influx into the CNS, as well as the severity of EAE. Autoreactive T cells purified from IL-21-treated mice transferred more severe EAE than did the control encephalitogenic T cells. No such effects were observed when IL-21 was administered after EAE progressed. Additional studies demonstrated that IL-21 given before the induction of EAE boosted NK cell function, including secretion of IFN-gamma. Depletion of NK cells abrogated the effect of IL-21. Therefore, IL-21, by affecting NK cells, has differential effects during the initiation and progression of autoimmune responses against neuroantigens.
Vollmer
Timothy L
TL
Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Liu
Ruolan
R
Price
Mary
M
Rhodes
Susan
S
La Cava
Antonio
A
Shi
Fu-Dong
FD
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002478:Cells, Cultured; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D007115:Immunization Schedule; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D000098546:Interleukin-21
D001323:Autoantibodies; D006023:Glycoproteins; D007378:Interleukins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma; D000098546:Interleukin-21