Interleukin-17 production and T helper 17 cells in peripheral blood mononuclear cells in response to ocular lysate in patients with birdshot chorioretinopathy

Mol Vis. 2013 Dec 27:19:2606-14. eCollection 2013.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Birdshot Chorioretinopathy
  • Case-Control Studies
  • Chorioretinitis / complications
  • Chorioretinitis / genetics
  • Chorioretinitis / immunology*
  • Chorioretinitis / pathology
  • Choroid / chemistry
  • Complex Mixtures / immunology
  • Complex Mixtures / pharmacology*
  • Female
  • Gene Expression
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • Humans
  • Inflammation / complications
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Male
  • Middle Aged
  • Primary Cell Culture
  • Retina / chemistry
  • Skin / chemistry
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / pathology

Substances

  • Complex Mixtures
  • HLA-A Antigens
  • HLA-A29 antigen
  • IL10 protein, human
  • Interleukin-17
  • Interleukin-10
  • Interferon-gamma