Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells

G M Verjans, L Remeijer, Cornelia M Mooy, A D Osterhaus

Research output: Contribution to journalArticleResearchpeer-review


PURPOSE: Herpetic stromal keratitis (HSK) is a T-cell-mediated inflammatory disease initiated by a herpes simplex virus (HSV) infection of the cornea. Recently, studies in the HSK mouse model have shown that the immunopathogenic T cells are directed against the HSV protein UL6 cross-reacting with an unknown corneal autoantigen. Whether this type of autoimmunity plays a role in human HSK was analyzed.

METHODS: T-cell lines (TCLs) were generated from corneal buttons of 12 patients with different clinical stages of HSV-induced necrotizing stromal keratitis (n = 9) or immune stromal keratitis (n = 3). The initiating virus was identified by polymerase chain reaction and immunohistology performed on the corneal buttons. Peripheral blood mononuclear cells (PBMCs) were isolated, and B cell lines (BLCLs) were generated by transformation with Epstein-Barr virus. Proliferative responses of these intracorneal TCLs were determined by culturing T cells with autologous BLCLs infected with HSV-1, HSV-2, wild-type vaccinia virus (VV-WT), or VV expressing HSV-1 UL6 (rVV-UL6). Alternatively, T cells were incubated with PBMCs pulsed with human cornea protein extract.

RESULTS: Irrespective of clinical diagnosis or treatment, T cells were recovered from the corneal buttons of all the 12 HSK patients. The intracorneal TCLs of 9 of the 12 HSK patients showed HSV-specific T-cell reactivity. In none of the TCLs, T-cell reactivity against HSV-1 UL6 or human corneal antigens was detected.

CONCLUSIONS: These data suggest that the potentially immunopathogenic intracorneal T-cell response in HSK patients is directed to the initiating virus and not to a human corneal autoantigen or HSV-1 UL6.

Original languageEnglish
Pages (from-to)2607-12
Number of pages6
JournalInvestigative ophthalmology & visual science
Issue number9
Publication statusPublished - Aug 2000


  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantigens/immunology
  • Autoimmunity/immunology
  • B-Lymphocytes/immunology
  • Cell Movement
  • Corneal Stroma/immunology
  • DNA, Viral/analysis
  • Epitopes/immunology
  • Female
  • Herpesvirus 1, Human/genetics
  • Herpesvirus 2, Human/immunology
  • Humans
  • Immunoenzyme Techniques
  • Immunophenotyping
  • Keratitis, Herpetic/immunology
  • Lymphocyte Activation/immunology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • T-Lymphocytes/immunology
  • Vaccinia virus/immunology


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