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

Hum Immunol. 2014 Jun;75(6):570-7. doi: 10.1016/j.humimm.2014.02.012. Epub 2014 Feb 12.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / pharmacology
  • Birdshot Chorioretinopathy
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology*
  • Chorioretinitis / immunology
  • Chorioretinitis / pathology*
  • Choroid / chemistry
  • Choroid / immunology
  • Choroid / pathology*
  • Complex Mixtures / pharmacology
  • Female
  • Gene Expression
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • Humans
  • Immunophenotyping
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Middle Aged
  • Primary Cell Culture
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Retina / chemistry
  • Retina / immunology
  • Retina / pathology*
  • Th1-Th2 Balance
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Vitreous Body / immunology
  • Vitreous Body / pathology*

Substances

  • Autoantigens
  • Complex Mixtures
  • HLA-A Antigens
  • HLA-A29 antigen
  • Receptors, Antigen, T-Cell, alpha-beta
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma