Purchase this article with an account.
L. BenMohamed, A. A. Chentoufi, G. Dasgupta, N. D. Christensen, J. Hu, Z. S. Choudhury, A. Azeem, J. V. Jester, S. L. Wechsler, A. B. Nesburn; Human CD8+ T-Cell Epitopes Protect HLA Transgenic Rabbits from Spontaneous Recurrent Ocular Herpes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3872.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Herpes simplex virus 1 (HSV-1) infects the cornea and then establishes latency in sensory neurons of the trigeminal ganglia (TG). Spontaneous reactivation of HSV-1 causes shedding of virus in tears which can result in recurrent Herpes Stromal Keratitis (HSK), a blinding ocular disease. A major gap in our knowledge is: "How to prevent or significantly reduce virus shedding and recurrent HSV eye disease?" HSV-specific CD8+ T-cells appear to decrease in vitro HSV-1 reactivation in explanted mouse TG. Unfortunately, spontaneous reactivation of HSV-1 in mice is extremely rare and recurrent HSK cannot be studied. In contrast, spontaneous reactivation occurs in rabbits and "humanized" HLA transgenic rabbits that mount "human-like" CD8 T-cell immune responses (HLA Tg rabbits) can be used to study protective efficacy of human CD8 T-cell epitopes against spontaneous reactivation and recurrent eye disease.
Latently infected HLA Tg rabbits were immunized subcutaneously 3X at 2 week intervals, with lipopeptides bearing HLA-A*0102-restricted gD epitopes. Control rabbits received saline. Ten days after the last immunization, HSV-specific CD8+ T-cell immune responses were analyzed in spleen, conjunctiva, and TG using a CFSE assay. The frequency of HSV peptide-specific CD8+ T-cells was measured using peptide-specific/HLA-A*0102 tetramers. The protective efficacy of asymptomatic CD8 T-cell epitopes against virus shedding in tears was analyzed.
(1) Immunization induced strong HSV-1 and peptide-specific CD8+ immune responses in spleen, conjunctiva and TG of HLA Tg rabbits. (2) Therapeutic immunization decreased spontaneous reactivation 4-fold (p < 0.0001). (3) Protective immunity correlated with the presence of local Granzyme B+, IFN-gamma+, CD8+ T-cells in TG and draining lymph nodes.
Therapeutic immunization with human CD8 T-cell gD epitopes can significantly reduce HSV-1 spontaneous recurrent shedding in HLA Tg rabbits. Protection appeared to correlate with induction of CD8 T-cells that produce GrB and IFN-gamma.
This PDF is available to Subscribers Only