Heterogeneity of EAE mediated by multiple distinct T-effector subsets.
Both T(H)1 and T(H)17 lymphocytes are implicated in inducing EAE. In mice lacking IFNgamma, T(H)17 are assumed to be the subset responsible for inflammation induction. Here, we demonstrate that IFNgamma KO mice have two additional effector subsets, one that up-regulates T(H)17-associated pro-inflammatory genes, but does not make IL-17 protein, and a second that utilizes IL-12-related elements of the T(H)1 pathway in an IFNgamma-independent manner. In vivo, these two subsets induce demonstrably different disease. By using homogeneous T cell lines, we can dissect the population of autoimmune effector cells, and demonstrate the multiplicity of pro-inflammatory pathways important in disease processes.
Abromson-Leeman
Sara
S
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. sara_abromson-leeman@hms.harvard.edu
Ladell
Daniel S
DS
Bronson
Roderick T
RT
Dorf
Martin E
ME
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency; D018664:Interleukin-12 / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D020381:Interleukin-17; D018992:Myelin-Associated Glycoprotein; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12; D007371:Interferon-gamma