Ocular Infiltrating CD4<sup>+</sup>T Cells from Patients with Vogt-Koyanagi-Harada Disease Recognize Human Melanocyte Antigens

Sugita, Sunao; Takase, Hiroshi; Taguchi, Chikako; Imai, Yasuhisa; Kamoi, Koju; Kawaguchi, Tatsushi; Sugamoto, Yoshiharu; Futagami, Yuri; Itoh, Kyogo; Mochizuki, Manabu

doi:10.1167/iovs.05-1547

Cited by 147 publications

(106 citation statements)

References 22 publications

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“…Human RPE cells with activated T cells significantly expressed IFN-c associated chemokines such as CXCL9, 10, and 11. 20 Immune attack eyes with iPS-RPE cells in animal models have also been found to have activated T lymphocytes as well as APC. 12 Moreover, the human in vitro immune response against iPS-RPE cells is also important for T-cell immunity, especially for the Th1 immune response.…”

Section: Discussionmentioning

confidence: 99%

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Sugita

Makabe

Fujii

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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METHODS. To confirm expression of complement factors in human iPS-RPE cells, we performed flow cytometry, immunohistochemistry, ELISA, and quantitative RT-PCR for the following: C3, C5, CFB (Factor B), C5b-9 (membrane attack complex [MAC]), CFH (Factor H), CFI (Factor I), CD46, CD55, CD59, clusterin, and vitronectin. We also prepared iPS-RPE cells in the presence of recombinant IFN-c, recombinant TNF-a, lipopolysaccharide, supernatants of naïve T cells, and T helper 1 (Th1) cells. For the transplantation, after preparation of iPS-RPE cells from cynomolgus monkeys, the iPS-RPE cells (allografts) were transplanted into the subretinal space in monkeys. After surgery, monkeys were euthanized for IHC evaluation of the retinal section and determination of complement factors (C3, C5, CFB, MAC, and C1q), cytokines, and immunoglobulin G (IgG). RESULTS. Human iPS-RPE cells expressed complement activators and inhibitors. iPS-RPE cellshighly expressed complement factors during inflammatory conditions, especially IFN-c exposure including Th1 cell supernatants. In immune attack eyes after allogeneic iPS-RPE cell transplantation, complement activators such as C3, CFB, C5, and MAC were detected around the host RPE layer, grafted RPE cells, inflammatory retinal lesions, and transplanted subretinal space. In addition, we observed a large number of C1q and IgG double positive and IFN-c positive inflammatory cells in the retinal sections.CONCLUSIONS. iPS-derived RPE cells greatly expressed complement factors. Thus, RPE cells might be activated and produce complement factors after exposure to infiltrating inflammatory cells in the eye.

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Section: Discussionmentioning

confidence: 99%

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Sugita

Makabe

Fujii

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…T cell clones (TCCs) were established by the limiting dilution method, as previously described (13,14). The cells were all CD4 + T cells obtained from patients with uveitis who had Behçet's disease (B2-3, B2-25, B25-16, B25-31, B25-48, B25-50, B26-2, B26-5), VKH disease (VKH37-1, VKH37-4), or HLA-B27 + AAU (AAU4-3, AAU4-6).…”

Section: Establishment Of T Cell Clones and T Cell Linesmentioning

confidence: 99%

“…Mice were immunized s.c. in the neck region with 200 mg IRBP peptide (IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ; GPTHLFQPSLVLDMAKVLLD; Bio-Synthesis) emulsified in CFA (Difco) containing Mycobacterium tuberculosis strain H37Ra (Difco) and injected i.p. with 100 ng pertussis toxin (Sigma) as an additional adjuvant (15,16).…”

Section: Induction Of Experimental Autoimmune Uveitismentioning

confidence: 99%

Role of IL-22– and TNF-α–Producing Th22 Cells in Uveitis Patients with Behçet’s Disease

Sugita

Kawazoe

Imai

et al. 2013

The Journal of Immunology

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Behçet’s disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet’s disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4+ T cells from the peripheral blood of Behçet’s disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti–TNF-α– and anti–IL-6–blocking Abs, Behçet’s disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22–producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet’s disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet’s disease.

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“…VKH pathogenesis in the eye is characterized by an autoimmune reaction against stromal melanocytes or associated proteins [5][6][7][8]. It is considered a primary stromal choroiditis because the inflammatory reaction electively starts within the choroidal stroma [9].…”

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Catching the therapeutic window of opportunity in early initial-onset Vogt–Koyanagi–Harada uveitis can cure the disease

et al. 2018

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Ocular Infiltrating CD4⁺T Cells from Patients with Vogt-Koyanagi-Harada Disease Recognize Human Melanocyte Antigens

Abstract: In VKH there are tyrosinase and gp100 peptide-specific T cells that can mediate an inflammatory response. Such melanocyte antigen-specific T cells could be associated with the cause and pathology of VKH disease.

Cited by 147 publications

References 22 publications

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Role of IL-22– and TNF-α–Producing Th22 Cells in Uveitis Patients with Behçet’s Disease

Catching the therapeutic window of opportunity in early initial-onset Vogt–Koyanagi–Harada uveitis can cure the disease

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Ocular Infiltrating CD4+T Cells from Patients with Vogt-Koyanagi-Harada Disease Recognize Human Melanocyte Antigens

Abstract: In VKH there are tyrosinase and gp100 peptide-specific T cells that can mediate an inflammatory response. Such melanocyte antigen-specific T cells could be associated with the cause and pathology of VKH disease.

Cited by 147 publications

References 22 publications

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Role of IL-22– and TNF-α–Producing Th22 Cells in Uveitis Patients with Behçet’s Disease

Catching the therapeutic window of opportunity in early initial-onset Vogt–Koyanagi–Harada uveitis can cure the disease

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Ocular Infiltrating CD4⁺T Cells from Patients with Vogt-Koyanagi-Harada Disease Recognize Human Melanocyte Antigens