Antigen-specific accumulation of naïve, memory and effector CD4 T cells during anterior uveitis monitored by intravital microscopy.
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.
Dullforce
Per A
PA
Department of Ophthalmology at Casey Eye Institute, Oregon Health & Science University, Portland, 97239, USA.
Seitz
Greg W
GW
Garman
Kiera L
KL
Michael
Julie A
JA
Crespo
Sergio M
SM
Fleischman
Ross J
RJ
Planck
Stephen R
SR
Parker
David C
DC
Rosenbaum
James T
JT
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*
D000941:Antigens; D018960:Hyaluronan Receptors; D039421:Integrin alpha2; D010047:Ovalbumin