Detection of antigen-specific T cells in experimental immune-mediated blepharoconjunctivitis in DO11.10 T cell receptor transgenic mice.
Antigen (Ag)-specific T cells are thought to play a key role in pathogenesis of chronic allergic conjunctivitis (AC) such as atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). In order to investigate the trafficking of Ag-specific T cells in experimental immune-mediated blepharoconjunctivitis (EC), we established a novel AC model in DO11.10 T cell receptor (TcR) transgenic (Tg) mice. DO11.10 TcR-Tg mice were challenged with eye drops of whole OVA protein, OVA peptide 1-15, 321-335, or 323-339. Their eyes were histologically examined. Conventional proliferation assay was performed against each Ag. Phenotypes of infiltrating cells and kinetics of Ag-specific T cells were investigated by immunohistochemistry. Adoptive transfer of CD4(+) Ag-specific T cells from DO11.10 TcR-Tg to WT mice was performed. The distribution of KJ1-26(+) cells was investigated in recipient mice. The challenge of OVA peptide 323-339 induced infiltration of inflammatory cells in conjunctivae in a dose dependent manner, accompanied by the proliferative responses of splenocytes. Immunohistochemical analysis revealed Agspecific/ non-Ag-specific T cells, macrophages, and eosinophils in conjunctivae. Infiltration of Ag-specific T cells increased 24 hr later. Transfer of CD4(+) cells from DO11.10 TcR-Tg to WT mice induced EC depending on the number of transferred cells. Ag-specific T cells were detected in the conjunctivae and spleens of recipient mice, though its numbers were significantly smaller compared to DO11.10 TcR-Tg mice. The challenge of OVA peptide 323-339 induced EC in DO11.10 TcR-Tg mice without prior sensitization. The response was mediated by CD4(+) Ag-specific T cells. The trafficking of Ag-specific T cells in EC was clearly visualized.
Ozaki
Akemi
A
Laboratory of Immunology, Department of Ophthalmology, Kochi Medical School, Japan.
Ishida
Waka
W
Fukata
Kazuyo
K
Fukushima
Atsuki
A
Ueno
Hisayuki
H
D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003228:Conjunctiva / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D051379:Mice; D008822:Mice, Transgenic; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*
D015415:Biomarkers; D039481:CD11b Antigen; C111390:OVA 323-339; D009883:Ophthalmic Solutions; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin