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.
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.
Authors: Anne Kelso; Elaine O Costelloe; Barbara J Johnson; Penny Groves; Kathy Buttigieg; David R Fitzpatrick Journal: Int Immunol Date: 2002-06 Impact factor: 4.823
Authors: Richard M Coles; Scott N Mueller; William R Heath; Francis R Carbone; Andrew G Brooks Journal: J Immunol Date: 2002-01-15 Impact factor: 5.422