Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes.
Experimental autoimmune encephalomyelitis (EAE) is a model of human multiple sclerosis induced by autoreactive Th cells that mediate tissue inflammation and demyelination in the CNS. Initially, IFN-gamma-producing Th1 cells and, more recently, IL-17-producing Th17 cells with specificity for myelin Ags have been implicated in EAE induction, but whether Th17 cells are encephalitogenic has been controversial. Moreover, a new effector T cell subset, Th9 cells, has been identified; however, the ability of this T cell subset to induce EAE has not been investigated. Here, we have developed protocols to generate myelin oligodendrocyte glycoprotein-specific Th17, Th1, Th2, and Th9 cells in vitro, so that we could directly compare and characterize the encephalitogenic activity of each of these subsets upon adoptive transfer. We show that myelin oligodendrocyte glycoprotein-specific Th1, Th17, and Th9 cells but not Th2 cells induce EAE upon adoptive transfer. Importantly, each T cell subset induced disease with a different pathological phenotype. These data demonstrate that different effector T cell subsets with specificity for myelin Ags can induce CNS autoimmunity and that the pathological heterogeneity in multiple sclerosis lesions might in part be due to multiple distinct myelin-reactive effector T cells.
Jäger
Anneli
A
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Dardalhon
Valérie
V
Sobel
Raymond A
RA
Bettelli
Estelle
E
Kuchroo
Vijay K
VK
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D020381:Interleukin-17 / Q000276:immunology; D016906:Interleukin-9 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation
D020381:Interleukin-17; D016906:Interleukin-9; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein