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Steffani Fitzpatrick, Robert Lausch, Robert A. Barrington; CCR6-Positive γδ T Cells Provide Protection Against Intracorneal HSV-1 Infection. Invest. Ophthalmol. Vis. Sci. 2019;60(12):3952-3962. doi: 10.1167/iovs.19-27810.
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© ARVO (1962-2015); The Authors (2016-present)
γδ T cells offer an important early immune defense against many different pathogens, both bacterial and viral. Herein, we examined the capacity of γδ T cell subsets to provide protection in the cornea against herpes simplex virus-1 (HSV-1).
C57Bl/6 (wild-type [WT]), γδ T-cell deficient (TCRδ−/−) and CCR6-deficient (CCR6−/−) mice were infected intracorneally with HSV-1. At multiple time points following infection, corneas were excised, and cells were immunostained for surface markers, intracellular cytokines, and analyzed using flow cytometry. WT and CCR6−/− γδ T cells were adoptively transferred into TCRδ−/− mice and corneal scores and survival were measured.
Intracorneal infection of mice lacking γδ T cells exhibited increased corneal opacity scores, elevated viral titers, and higher mortality compared with WT mice. Both CCR6+ and CCR6neg γδ T cell subsets were observed in corneas after virus infection. CCR6+ γδ T cells produced IL-17A and were predominantly CD44+CD62L+, consistent with natural IL-17+ γδ T cells. In contrast IL-17A production by CCR6neg γδ T cells was infrequent, and this subset was largely single positive for CD62L or CD44. The CCR6+ subset appeared to provide protection against HSV-1 as follows: (1) CCR6−/− mice had more severe corneal opacity compared with WT mice; and (2) adoptive transfer of γδ T cells from WT mice restored protection in TCRδ−/− mice whereas transfer of γδ T cells from CCR6−/− mice did not.
γδ T cells in the cornea can be divided into CCR6+ and CCR6neg subsets with the former conferring protection early after intracorneal HSV-1 infection.
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