Detection of choroid- and retina-antigen reactive CD8+ and CD4+ T lymphocytes in the vitreous fluid of patients with birdshot chorioretinopathy

Jonas J W Kuiper, Aniki Rothova, Peter A W Schellekens, Annette Ossewaarde-van Norel, Andries C. Bloem, Tuna Mutis

    Research output: Contribution to journalArticleAcademicpeer-review

    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.

    Original languageEnglish
    Pages (from-to)570-577
    Number of pages8
    JournalHuman Immunology
    Volume75
    Issue number6
    DOIs
    Publication statusPublished - 1 Jan 2014

    Cite this

    Kuiper, Jonas J W ; Rothova, Aniki ; Schellekens, Peter A W ; Ossewaarde-van Norel, Annette ; Bloem, Andries C. ; Mutis, Tuna. / Detection of choroid- and retina-antigen reactive CD8+ and CD4+ T lymphocytes in the vitreous fluid of patients with birdshot chorioretinopathy. In: Human Immunology. 2014 ; Vol. 75, No. 6. pp. 570-577.
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    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.",
    author = "Kuiper, {Jonas J W} and Aniki Rothova and Schellekens, {Peter A W} and {Ossewaarde-van Norel}, Annette and Bloem, {Andries C.} and Tuna Mutis",
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    Detection of choroid- and retina-antigen reactive CD8+ and CD4+ T lymphocytes in the vitreous fluid of patients with birdshot chorioretinopathy. / Kuiper, Jonas J W; Rothova, Aniki; Schellekens, Peter A W; Ossewaarde-van Norel, Annette; Bloem, Andries C.; Mutis, Tuna.

    In: Human Immunology, Vol. 75, No. 6, 01.01.2014, p. 570-577.

    Research output: Contribution to journalArticleAcademicpeer-review

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    AU - Kuiper, Jonas J W

    AU - Rothova, Aniki

    AU - Schellekens, Peter A W

    AU - Ossewaarde-van Norel, Annette

    AU - Bloem, Andries C.

    AU - Mutis, Tuna

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    N2 - 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.

    AB - 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.

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