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R.L. Hendricks, K. Prabhakaran; Regulation of CD8+ T Cell Effector Function by Herpes Simplex Virus Latently Infected Neurons . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3541.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recurrent herpes simplex virus type 1 (HSV–1)–induced keratitis results from reactivation of latent virus in the trigeminal ganglion (TG). We have shown that HSV gB498–505 –specific CD8+ T cells can block HSV–1 reactivation from latency through two effector mechanisms; interferon gamma (IFN–γ) and a previously undefined second mechanism. Here we define the second mechanism and an interesting regulatory pathway. Methods: Ex vivo cultures of latently infected TG were incubated for varying periods with or without gB498–505 pulsed target cells or anti–Qa1 mAb, and then stained simultaneously for CD107a (identifies cells that recently degranulated) and intracellular IFN–γ. In addition, CD8+ T cells in the TG were stained for CD94/NKG2a and neurons for Qa1. Results: CD8+ T cells in latently infected TG simultaneously produced IFN–γ and exocytosed lytic granules in response to gB498–505 pulsed target cells, but preferentially produced IFN–γ in response to latently infected neurons. All CD8+ T cells expressed CD94/NKG2a and a subpopulation of neurons expressed Qa1. Selective inhibition of lytic granule exocytosis was abrogated in the presence of anti–Qa1 mAb. Conclusions: Subpopulations of latently infected neurons are selectively protected from reactivation by CD8+ T cells either through IFN–γ or through lytic granules. Those that are selectively responsive to IFN–γ appear to inhibit lytic granule exocytosis through a Qa1–NKG2a inhibitory mechanism.
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