title: Both Th1 and Th17 are immunopathogenic but differ in other key biological activities.
abstract: The role of Th17 lymphocytes in immunopathogenic processes has been well established, but little is known about their basic cell features. In this study, we compared polarized Th1 and Th17 for key biological activities related to pathogenicity and trafficking. Th1 and Th17 lineages were derived from TCR-transgenic CD4 murine cells specific against hen egg lysozyme. When adoptively transferred into mice expressing hen egg lysozyme in their eyes, both Th1 and Th17 induced ocular inflammation but with slight differences in histological pathology. PCR analysis revealed selective expression of IFN-gamma or IL-17 in eyes of Th1 or Th17 recipients, respectively. Additionally, Th1 and Th17 were found to differ in three other key activities: 1) Th17 cells were inferior to Th1 cells in their capacity to trigger massive lymphoid expansion and splenomegaly; 2) the proportion of Th1 cells among infiltrating cells in inflamed recipient eyes declined rapidly, becoming a minority by day 7, whereas Th17 cells remained in the majority throughout this period; and 3) remarkable differences were noted between Th1 and Th17 cells in their expression of certain surface markers. In particular, reactivated Th1 expressed higher levels of CD49d and alpha(4)beta(7) (mucosal homing) in vitro and higher levels of CXCR3 (Th1 trafficking) in vivo. Reactivated Th17, however, expressed higher levels of alpha(E)beta(7) (epithelial tissue homing) and CD38 (activation, maturation and trafficking) in vitro, but in vivo Th17 expressed higher levels of alpha(4)beta(7) and CCR6 (lymphocyte trafficking). These data reveal that Th1 and Th17 cells differ in several key biological activities influencing migration and pathogenic behavior during inflammatory disease.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institute of Health, Bethesda, MD 20892, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cox
authors.forename: Guangpu
authors.initials: G
authors.lastname: Shi
authors.forename: Hongen
authors.initials: H
authors.lastname: Yin
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Vistica
authors.forename: Eric F
authors.initials: EF
authors.lastname: Wawrousek
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Igal
authors.initials: I
authors.lastname: Gery
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism*; D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D005128:Eye Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D054367:Receptors, CXCR3 / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: C515188:Cxcr3 protein, mouse; D016207:Cytokines; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D054367:Receptors, CXCR3; D007371:Interferon-gamma; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1