Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells
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.
|Keywords||*Cell Movement, Adult, Aged, Aged, 80 and over, Autoantigens/immunology, Autoimmunity/immunology, B-Lymphocytes/immunology/virology, Corneal Stroma/*immunology/pathology/virology, DNA, Viral/analysis, Epitopes/immunology, Female, Herpesvirus 1, Human/genetics/*immunology, Herpesvirus 2, Human/immunology, Humans, Immunoenzyme Techniques, Immunophenotyping, Keratitis, Herpetic/*immunology/pathology/virology, Lymphocyte Activation/immunology, Male, Middle aged, Polymerase Chain Reaction, Research Support, Non-U.S. Gov't, T-Lymphocytes/*immunology, Vaccinia virus/immunology|
Remeijer, L., Mooy, C.M., Osterhaus, A.D.M.E., & Verjans, G.M.G.M.. (2000). Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells. Investigative Ophthalmology & Visual Science. Retrieved from http://hdl.handle.net/1765/9438