title: Activated gammadelta T cells promote the activation of uveitogenic T cells and exacerbate EAU development.
abstract: OBJECTIVE
  To determine how the activation of γδ T cells affects the generation of uveitogenic αβ T cells and the development of experimental autoimmune uveitis (EAU).
  
  
  METHODS
  γδ T cells were isolated from B6 mice immunized with the uveitogenic peptide IRBP(1-20) and αβ T cells from immunized TCR-δ(-/-) mice. Resting γδ T cells were prepared by culture of separated γδ T cells in cytokine-free medium for 3 to 5 days, when they showed downregulation of CD69 expression. Activated γδ T cells were prepared by incubating resting γδ T cells with anti-γδ TCR (GL3) for 2 days. Responder αβ T cells were cocultured with immunizing antigen and antigen-presenting cells. The numbers of antigen-specific T cells expressing IL-17 or IFN-γ were determined by intracellular staining followed by FACS analysis after stimulation, with or without the addition of purified γδ T cells. The cytokines in the culture medium were measured by ELISA.
  
  
  RESULTS
  Highly enriched γδ T cells exert widely different effects on autoreactive αβ T cells in EAU, depending on the activation status of the γδ T cells. Whereas nonactivated γδ T cells had little effect on the activation of interphotoreceptor retinoid-binding protein-specific αβ T cells in vitro and in vivo, activated γδ T cells promoted the generation of uveitogenic T cells and exacerbated the development of EAU.
  
  
  CONCLUSIONS
  The functional ability of γδ T cells is greatly influenced by their activation status. Activated γδ T cells exacerbate EAU through increased activation of uveitogenic T cells.
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Nian
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D005136:Eye Proteins / Q000276:immunology / Q000494:pharmacology; D005260:Female; D020381:Interleukin-17 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000494:pharmacology; D012720:Severity of Illness Index; D013047:Specific Pathogen-Free Organisms; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D020381:Interleukin-17; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial