title: Interleukin-17 production and T helper 17 cells in peripheral blood mononuclear cells in response to ocular lysate in patients with birdshot chorioretinopathy.
abstract: OBJECTIVE
  To determine the cytokine response to ocular lysates of peripheral blood mononuclear cells (PBMCs) from patients with birdshot chorioretinopathy (BSCR).
  
  
  METHODS
  In the PBMCs of 19 patients with BSCR, T cell cytokine production in response to human retina and choroid lysates was analyzed with flow cytometry and compared to the responses against skin lysates. Five patients had active disease and had not yet been treated (naïve to systemic therapy); 14 patients had either immunomodulatory therapy (IMT) or inactive disease (referred as inactive/IMT). The PBMCs of 11 HLA-A29-positive healthy individuals were used as controls.
  
  
  RESULTS
  The levels of interleukin-17 (IL-17) in supernatant of cultures stimulated with retina lysate were higher in patients with active BSCR compared to the HLA-A29 positive controls. The levels of other T cell cytokines (IL-10 and interferon-γ [IFN-γ]) in PBMC cultures did not change significantly after stimulation with ocular lysate. The frequency of CD4(+) IL-17(+) (T helper 17 [Th17]) T cells but not of CD4(+) IFN-γ (Th1) T cells was elevated in the PBMCs of patients with active BSCR stimulated by retina lysates compared to skin lysates.
  
  
  CONCLUSIONS
  Our data demonstrate that PBMCs exhibit an IL-17-mediated immune response to retina lysate in patients with active disease naïve to systemic therapy. This is accompanied by the enrichment of IL-17-producing CD4(+) T cells. These findings support the current concept of chronic Th17-cell mediated inflammation and provide evidence that links the Th17 signatures to ocular-specific immune responses in BSCR.
authors.affiliation: Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands ; Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jonas J W
authors.initials: JJ
authors.lastname: Kuiper
authors.affiliation: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maarten E
authors.initials: ME
authors.lastname: Emmelot
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Aniki
authors.initials: A
authors.lastname: Rothova
authors.affiliation: Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Tuna
authors.initials: T
authors.lastname: Mutis
mesh_terms: D000328:Adult; D000368:Aged; D000080365:Birdshot Chorioretinopathy; D016022:Case-Control Studies; D002825:Chorioretinitis / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002829:Choroid / Q000737:chemistry; D045424:Complex Mixtures / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D012160:Retina / Q000737:chemistry; D012867:Skin / Q000737:chemistry; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D045424:Complex Mixtures; D015234:HLA-A Antigens; C035524:HLA-A29 antigen; C508609:IL10 protein, human; D020381:Interleukin-17; D016753:Interleukin-10; D007371:Interferon-gamma