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Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells.
Invest Ophthalmol Vis Sci 2000; 41(9):2607-12IO

Abstract

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.

Authors+Show Affiliations

Rotterdam Eye Hospital, Institute of Virology, Erasmus University Rotterdam, The Netherlands. verjans@viro.fgg.eur.nlNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10937573

Citation

Verjans, G M., et al. "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, vol. 41, no. 9, 2000, pp. 2607-12.
Verjans GM, Remeijer L, Mooy CM, et al. Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells. Invest Ophthalmol Vis Sci. 2000;41(9):2607-12.
Verjans, G. M., Remeijer, L., Mooy, C. M., & Osterhaus, A. D. (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, 41(9), pp. 2607-12.
Verjans GM, et al. Herpes Simplex Virus-specific T Cells Infiltrate the Cornea of Patients With Herpetic Stromal Keratitis: No Evidence for Autoreactive T Cells. Invest Ophthalmol Vis Sci. 2000;41(9):2607-12. PubMed PMID: 10937573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells. AU - Verjans,G M, AU - Remeijer,L, AU - Mooy,C M, AU - Osterhaus,A D, PY - 2000/8/11/pubmed PY - 2000/8/19/medline PY - 2000/8/11/entrez SP - 2607 EP - 12 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 41 IS - 9 N2 - 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. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/10937573/Herpes_simplex_virus_specific_T_cells_infiltrate_the_cornea_of_patients_with_herpetic_stromal_keratitis:_no_evidence_for_autoreactive_T_cells_ L2 - http://iovs.arvojournals.org/article.aspx?volume=41&page=2607 DB - PRIME DP - Unbound Medicine ER -