title: Antigen-specific accumulation of naïve, memory and effector CD4 T cells during anterior uveitis monitored by intravital microscopy.
abstract: Uveitis is an immune-mediated ocular disease and a leading cause of blindness. We characterized a novel model of uveitis with intravital microscopy. Transfer of ovalbumin-specific T cells from DO11.10 spleen to BALB/c recipients and subsequent challenge with ovalbumin in the anterior chamber of the eye resulted in anterior uveitis. Antigen-specificity was verified by injection of irrelevant antigen and transfer of T cells with a different specificity. Subsets of CD4 T cells, including naive (DO11.10 RAG(-/-)) and in vitro-activated Th2 effector CD4 T cells, infiltrated anterior segment tissues early in the inflammation. Memory-like CD44(high) CD4 T cells from unprimed transgenic mice and in vitro-activated Th1 effector CD4 T cells accumulated to larger numbers than naive or Th2 effector cells at 48 and 72 h. Of these, the alpha(2)-integrin+CD4 unprimed T cells entered the eye more efficiently, and antibody to alpha(2)-integrin markedly inhibited the inflammatory response. Intravital microscopy revealed the early arrival and antigen-specific accumulation of CD4 T cells in inflamed tissue and should be helpful in understanding T cell migration to other organs.
authors.affiliation: Department of Ophthalmology at Casey Eye Institute, Oregon Health & Science University, Portland, 97239, USA.
authors.forename: Per A
authors.initials: PA
authors.lastname: Dullforce
authors.forename: Greg W
authors.initials: GW
authors.lastname: Seitz
authors.forename: Kiera L
authors.initials: KL
authors.lastname: Garman
authors.forename: Julie A
authors.initials: JA
authors.lastname: Michael
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Crespo
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Fleischman
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
authors.forename: David C
authors.initials: DC
authors.lastname: Parker
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation; D018960:Hyaluronan Receptors / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D039421:Integrin alpha2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008853:Microscopy; D010047:Ovalbumin / Q000494:pharmacology; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000941:Antigens; D018960:Hyaluronan Receptors; D039421:Integrin alpha2; D010047:Ovalbumin