Herpes Research Today is a free monthly online journal that collates and summarizes the latest research about Herpes, including details on herpes simplex virus (hsv), genital, oral, symptoms, treatment.

Modulation of CD8+ CTL effector function by fibroblasts derived from the immunoprivileged cornea.

Knickelbein JE, Divito S, Hendricks RL

Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

PURPOSE: To examine the acquisition of lytic activity and interferon gamma (IFN-gamma) production by herpes simplex virus (HSV) type 1-specific CD8(+) cytotoxic T-lymphocyte precursors (HSV-CTLps) after exposure to in vitro HSV-1-infected fibroblasts derived from the immunoprivileged cornea (HSV-cFb) or nonprivileged skin (HSV-sFb) or to in vitro HSV-1-infected splenocytes (HSV-Spls) obtained from noninfected mice. METHODS: Chromium release assays were used to assess HSV-CTL cytotoxicity, and flow cytometry was used to assess intracellular granzyme (Gr) B content and lytic granule exocytosis through surface CD107a expression. In addition, the BLT esterase assay was used to assess functional GrA release. [(3)H]-Thymidine incorporation and total CD8(+) cell numbers, as assessed by flow cytometry, were used to assess CTLp proliferation. ELISA and intracellular flow cytometric analysis were used to assess CTL IFN-gamma production and release. RESULTS: HSV-cFb, HSV-sFb, and HSV-Spl individually induced strong cytotoxic and IFN-gamma responses by HSV-CTL. Simultaneous exposure to HSV-Spl and HSV-cFb virtually abrogated the cytotoxic response while enhancing IFN-gamma production by HSV-CTL. In contrast, exposure to HSV-sFb, in conjunction with HSV-Spl, did not alter the cytotoxic or IFN-gamma response of HSV-CTL compared with stimulation with either cell type alone. Abrogation of the cytotoxic response after simultaneous exposure to HSV-Spl and HSV-cFb was associated with reduced production, storage, or both of GrA and GrB but with unimpaired lytic granule release. CONCLUSIONS: These findings suggest that an interesting regulatory circuit protects the cornea from the potentially damaging effects of CD8(+) T-cell cytotoxic function while maintaining their ability to control virus replication through enhanced production of the antiviral cytokine IFN-gamma.

Published 26 April 2007 in Invest Ophthalmol Vis Sci, 48(5): 2194-202.
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