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This Article Full Text (PDF) All Versions of this Article: jimmunol.0901906v1 183/11/7169    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Jäger, A. Articles by Kuchroo, V. K. PubMed PubMed Citation Articles by Jäger, A. Articles by Kuchroo, V. K.

Th1, Th17, and Th9 Effector Cells Induce Experimental Autoimmune Encephalomyelitis with Different Pathological Phenotypes¹

Anneli Jäger,^* Valérie Dardalhon, Raymond A. Sobel, Estelle Bettelli,²³ and Vijay K. Kuchroo^3*

*Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139; and Palo Alto Veteran's Administration Health Care System and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305

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--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.

Correspondence: ³ Address correspondence and reprint requests to Dr. Estelle Bettelli, Benaroya Research Institute, Seattle, WA 98101. E-mail address: ebettelli{at}benaroyaresearch.org or Dr. Vijay K. Kuchroo, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115. E-mail address: vkuchroo{at}rics.bwh.harvard.edu

¹ This work was supported by grants from the National Institutes of Health (1R01NS059996 to E.B. and R01NS045937, R01NS035685, R37NS030843, R01A1044880, P01A1039671, and P01NS038037 and a Javits Neuroscience Investigator Award to V.K.K.) and the National Multiple Sclerosis Society (NMSS Transition Award TA3014A1/1) to E.B. and FG1642-A-1 to V.D. and RG-2571 to V.K.K. A.J. is the recipient of a Ph.D. scholarship by the Boehringer Ingelheim Fonds.

² Current address: Benaroya Research Institute, Seattle, WA 98101.