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 immunopathoge nic T cells are directed against the HSV protein UL6 cross-reacting with an unknown corneal autoantigen. Whether this type of autoimmunity plays a rol e in human HSK was analyzed. METHODS. T-cell lines (TCLs) were generated from corneal buttons of 12 pati ents with different clinical stages of HSV-induced necrotizing stromal kera titis (n = 9) or immune stromal keratitis (n = 3). The initiating virus was identified by polymerase chain reaction and immunohistology performed on t he corneal buttons. Peripheral blood mononuclear cells (PBMCs) mere isolate d, and B cell lilies (BLCLs) were generated by transformation with Epstein- Barr virus. Proliferative responses of these intracorneal TCLs were determi ned 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). Alt ernatively, T cells were incubated with PBMCs pulsed with human cornea prot ein extract. RESULTS. Irrespective of clinical diagnosis or treatment, T cells were reco vered 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 ant igens was detected. CONCLUSIONS. These data suggest that the potentially immunopathogenic intra corneal T-cell response in HSK patients is directed to the initiating virus and not to a human corneal autoantigen or HSV-1 UL6.