title: Detection of choroid- and retina-antigen reactive CD8(+) and CD4(+) T lymphocytes in the vitreous fluid of patients with birdshot chorioretinopathy.
abstract: Birdshot chorioretinopathy (BSCR), a progressive form of non-infectious uveitis, is the strongest HLA-associated disease described to date, with >95% of the patients displaying HLA-A29. Since indirect evidence indicates the involvement of T cells in the etiopathology of the disease, we now isolated, cultured and analyzed the vitreous fluid-infiltrating T cells from two BSCR patients with respect to their phenotype, cytokine profile, clonal distribution and antigen specificity. Phenotypic analyses revealed the predominant presence of both CD4(+) and CD8(+) T cells in vitreous fluid. Further analyses on short term expanded and cloned T cells suggested that eye-infiltrating T cells generally displayed a Th1 like cytokine profile with secretion of high levels of IFN-γ and TNF-α. In one patient an oligoclonal CD4(+) and CD8(+) T cell infiltration, with a moderate to strongly skewed TCR Vβ usage was suggestive for an antigen driven infiltration/expansion. Indeed, a number of intraocular CD4(+) and CD8(+) T cells responded to crude retinal and choroidal lysates. These results, which demonstrate for the first time the existence of eye-antigen-specific T cells in the vitreous fluid of BSCR patients, substantiate the current view on the role of eye-antigen specific T cells in the etiopathology of BSCR.
authors: Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: J.J.W.Kuiper@umcutrecht.nl.
authors: Jonas J W
authors: JJ
authors: Kuiper
authors: Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Department of Ophthalmology, Erasmus Medical Center Rotterdam, Doctor Molewaterplein 50-60, 3015 GJ Rotterdam, The Netherlands.
authors: Aniki
authors: A
authors: Rothova
authors: Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors: Peter A W
authors: PA
authors: Schellekens
authors: Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors: Annette
authors: A
authors: Ossewaarde-van Norel
authors: Department of Medical Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors: Andries C
authors: AC
authors: Bloem
authors: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors: Tuna
authors: T
authors: Mutis
mesh_terms: D001324:Autoantigens / Q000494:pharmacology; D000080365:Birdshot Chorioretinopathy; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002825:Chorioretinitis / Q000276:immunology / Q000473:pathology*; D002829:Choroid / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D045424:Complex Mixtures / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D061251:Primary Cell Culture; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D012160:Retina / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D058408:Th1-Th2 Balance; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014822:Vitreous Body / Q000276:immunology / Q000473:pathology*
chemical_list: D001324:Autoantigens; D045424:Complex Mixtures; D015234:HLA-A Antigens; C035524:HLA-A29 antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma