title: Unlike Th1, Th17 cells mediate sustained autoimmune inflammation and are highly resistant to restimulation-induced cell death.
abstract: Both Th1 and Th17 T cell subsets can mediate inflammation, but the kinetics of the pathogenic processes mediated by these two subsets have not been investigated. Using an experimental system in which TCR-transgenic Th1 or Th17 cells specific for hen egg lysozyme induce ocular inflammation in recipient mice expressing eye-restricted hen egg lysozyme, we found important differences in the in vivo behavior of these two subsets. Th1 cells initially proliferated considerably faster and invaded the eye more quickly than their Th17 counterparts, but then disappeared rapidly. By contrast, Th17 cells accumulated and remained the majority of the infiltrating CD4(+) cells in the eye for as long as 25 days after transfer, mediating more long-lasting pathological changes. Unlike Th1, Th17 cells were highly resistant to restimulation-induced apoptosis, a major pathway by which autoimmune and chronically restimulated Th1 cells are eliminated. Th17 cells had reduced Fas ligand production and resistance to Fas-induced apoptosis, relative to Th1 cells, despite similar surface expression of Fas. Th17-induced ocular inflammation also differed from Th1-induced inflammation by consisting of more neutrophils, whereas Th1-induced disease had higher proportions of CD8 cells. Taken together, our data show that pathogenic processes triggered by Th17 lag behind those induced by Th1, but then persist remarkably longer, apparently due to the relative resistance of Th17 cells to restimulation-induced cell death. The long-lasting inflammation induced by Th17 cells is in accord with these cells being involved in chronic conditions in humans.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Guangpu
authors.initials: G
authors.lastname: Shi
authors.forename: Madhu
authors.initials: M
authors.lastname: Ramaswamy
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Vistica
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cox
authors.forename: Cuiyan
authors.initials: C
authors.lastname: Tan
authors.forename: Eric F
authors.initials: EF
authors.lastname: Wawrousek
authors.forename: Richard M
authors.initials: RM
authors.lastname: Siegel
authors.forename: Igal
authors.initials: I
authors.lastname: Gery
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D002455:Cell Division; D005123:Eye / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D020381:Interleukin-17; D019014:fas Receptor; D009113:Muramidase