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. 2003 Feb;77(3):1877-84.
doi: 10.1128/jvi.77.3.1877-1884.2003.

"V体育ios版" Activation of natural killer (NK) T cells during murine cytomegalovirus infection enhances the antiviral response mediated by NK cells

Serani L H van Dommelen  1 , Hyacinth A Tabarias, Mark J Smyth, Mariapia A Degli-Esposti
Affiliations

Activation of natural killer (NK) T cells during murine cytomegalovirus infection enhances the antiviral response mediated by NK cells

Serani L H van Dommelen et al. J Virol. 2003 Feb.

VSports在线直播 - Abstract

NK1. 1+ T (NKT) cells are efficient regulators of early host responses which have been shown to play a role in tumor surveillance. The relevance of NKT cells in immune surveillance of viral infections, however, is not well understood. In this study, we investigated the functional relevance of NKT cells in controlling herpesvirus infections by using challenge with murine cytomegalovirus (MCMV) as the study model. This model has proven to be one of the best systems for evaluating the role of NK cells during virus infection VSports手机版. Using gene-targeted mice and alpha-galactosylceramide (alpha-GalCer) as an exogenous stimulator of NKT cells, we have analyzed the role of these cells in the immune surveillance of MCMV infection. Our studies in NKT-cell-deficient, T-cell receptor Jalpha281 gene-targeted mice have established that classical NKT cells do not play a critical role in the early clearance of MCMV infection. Importantly, however, activation of NKT cells by alpha-GalCer resulted in reduced viral replication in visceral organs. Depletion studies, coupled with analysis of gene-targeted mice lacking perforin and gamma interferon (IFN-gamma), have revealed that the antiviral effects of alpha-GalCer involve NK cells and have clearly demonstrated that the antiviral activity of alpha-GalCer, unlike the antitumor one, is critically dependent on both perforin and IFN-gamma. .

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"V体育平台登录" Figures

FIG. 1.
FIG. 1.
α-GalCer therapy reduces MCMV replication in BALB/c mice. MCMV-susceptible BALB/c mice were inoculated i.p. with 104 PFU of MCMV and treated with 2 μg of α-GalCer on days 0 and 4. Virus titers in the spleen, liver, lung, and salivary gland are shown. The solid line represents α-GalCer-treated mice, and the dashed line represents vehicle-treated mice. The dashed line across the graph indicates the limit of detection of the assay. Results are presented as log means ± SEM from 15 mice per group and were derived by combining data from 5 independent experiments, each utilizing 3 mice per group. **, P < 0.001; *, P ≤ 0.05.
FIG. 2.
FIG. 2.
MCMV replication in B6 mice treated with α-GalCer. MCMV-resistant B6 mice were inoculated i.p. with 105 PFU of MCMV and treated with 2 μg of α-GalCer on days 0 and 4. Virus titers in the spleen and liver are shown. Solid lines represent α-GalCer-treated mice, and dashed lines represent vehicle-treated mice. The dashed line across the graph indicates the limit of detection of the assay. Results are presented as log means ± SEM from 6 mice per group and were derived by combining data from duplicate independent experiments, each utilizing 3 mice per group. **, P < 0.005; *, P < 0.01.
FIG. 3.
FIG. 3.
Replication of MCMV in NKT-cell-deficient B6.Jα281−/− mice. B6.Jα281−/− and B6 mice were inoculated i.p. with 104 PFU of MCMV. Virus titers in the spleen and liver are shown. Solid squares represent B6.Jα281−/− mice, and open squares represent B6 WT mice. The dashed line across the graph indicates the limit of detection of the assay. Results are presented as log means ± SEM from 12 mice per group and were derived by combining data from 4 independent experiments, each utilizing 3 mice per group. **, P < 0.005.
FIG. 4.
FIG. 4.
Replication of MCMV in NKT-cell-deficient B6.Jα281−/− mice with and without α-GalCer therapy. (A) B6.Jα281−/− mice were inoculated i.p. with 104 PFU of MCMV and treated with 2 μg of α-GalCer on days 0 and 4. Virus titers in the spleen and liver are shown. Solid squares represent α-GalCer-treated mice, and open squares represent vehicle-treated mice. The dashed line across the graph indicates the limit of detection of the assay. (B) B6.Jα281−/− mice were inoculated i.p. with 105 PFU of MCMV and treated with 2 μg of α-GalCer on days 0 and 4. Virus titers in the spleen and liver at day 2 p.i. are shown. Results are presented as log means ± SEM from 6 mice per group and were derived by combining data from duplicate independent experiments, each utilizing 3 mice per group.
FIG. 5.
FIG. 5.
NK cells are the major effectors in improved MCMV clearance mediated by α-GalCer therapy. BALB/c mice were depleted of NK cells by the administration of three doses of anti-asialoGM1 (α-aGM1) on days −1, 0, and 6 relative to MCMV inoculation. Mice were then inoculated i.p. with 104 PFU of MCMV and treated with 2 μg of α-GalCer on days 0 and 4. Virus titers in the spleen and liver are shown. The dashed line across the graph indicates the limit of detection of the assay. Results are presented as log means ± SEM from 12 mice per group and were derived by combining data from 4 independent experiments, each utilizing 3 mice per group. , P < 0.005 when groups 1 and 2 are compared; ¤, P < 0.005 when groups 2 and 4 are compared; ***, P < 0.0005 when groups 3 and 4 are compared; **, P < 0.005 when groups 3 and 4 are compared; *, P < 0.05 when groups 3 and 4 are compared.
FIG. 6.
FIG. 6.
Role of perforin and IFN-γ in the improved MCMV clearance mediated by α-GalCer therapy. Mice were inoculated i.p. with 104 PFU of MCMV and treated with 2 μg of α-GalCer on days 0 and 4. Virus titers in the spleen, liver, and lung are shown. Squares represent α-GalCer-treated mice, and triangles represent vehicle-treated mice. Results are presented as means ± SEM of at least 3 mice per group and are representative of duplicate independent experiments. **, P < 0.005; *, P < 0.05.
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