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Journal of Virology, October 2005, p. 12798-12806, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12798-12806.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

T-bet Is Required for Protection against Vaccinia Virus Infection

Masanori Matsui,^1* Osamu Moriya,¹ Takayuki Yoshimoto,² and Toshitaka Akatsuka¹

Department of Microbiology, Saitama Medical School, Saitama,¹ Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan²

Received 13 June 2005/ Accepted 29 July 2005

The transcription factor T-bet regulates the differentiation of CD4⁺ T-helper type 1 (Th1) cells and represses Th2 lineage commitment. Since Th1 cells are crucial in the defense against pathogens, several studies addressed the role of T-bet in immunity to infection using T-bet knockout (T-bet^–/–) mice. Nevertheless, it is still unclear whether T-bet is required for defense. Although vaccinia virus (VV) has extensively been used as an expression vector and the smallpox vaccine, there is only limited knowledge about immunity to VV infection. The urgency to understand the immune responses has been increased because of concerns about bioterrorism. Here, we show that T-bet is critical in the defense against VV infection as follows: (i) the survival rate of T-bet^–/– mice was lower than that of control littermates postinfection; (ii) T-bet^–/– mice lost more weight postinfection; and (iii) control mice cleared VV faster than T-bet^–/– mice. As expected, a significant Th2 shift was observed in CD4⁺ T cells of T-bet^–/– mice. Furthermore, absence of T-bet impaired VV-specific CD8⁺ cytotoxic T-lymphocyte (CTL) function, including cytolytic activity, antiviral cytokine production, and proliferation. Cytolytic capacity of natural killer (NK) cells was also diminished in T-bet^–/– mice, whereas anti-VV antibody production was not impaired. These data reveal that the enhanced susceptibility to VV infection in T-bet^–/– mice was at least partially due to the Th2 shift of CD4⁺ T cells and the diminished function of VV-specific CTLs and NK cells but not due to downregulation of antibody production.

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* Corresponding author. Mailing address: Department of Microbiology, Saitama Medical School, Moroyama-Cho, Iruma-Gun, Saitama 350-0495, Japan. Phone: 81-49-276-1166. Fax: 81-49-295-9107. E-mail: mmatsui{at}saitama-med.ac.jp.

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Journal of Virology, October 2005, p. 12798-12806, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12798-12806.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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