Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells.
OBJECTIVE
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.
Rotterdam Eye Hospital, Institute of Virology, Erasmus University Rotterdam, The Netherlands. verjans@viro.fgg.eur.nl
G M
GM
Verjans
L
L
Remeijer
C M
CM
Mooy
A D
AD
Osterhaus
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D002465:Cell Movement; D003319:Corneal Stroma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D000939:Epitopes / Q000276:immunology; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology
D001324:Autoantigens; D004279:DNA, Viral; D000939:Epitopes