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OX40 Drives Protective Vaccinia Virus-Specific CD8 T Cells^1,2

Shahram Salek-Ardakani^3,*, Magdalini Moutaftsi, Shane Crotty, Alessandro Sette and Michael Croft^3,*

^* Division of Molecular Immunology and Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, San Diego, CA 92037

Vaccinia virus (VACV) affords long-lasting protection against variola virus, the agent of smallpox. VACV-reactive CD8 T cells contribute to protection but their molecular control is unknown. We show that the TNFR molecule OX40 (CD134) controls primary VACV-specific CD8 T cell expansion and antiviral cytokine production and dictates development of strong memory to both dominant and subdominant VACV epitopes. Using adoptive transfer of OX40-deficient CD8 TCR-transgenic T cells responding to Ag in the context of VACV infection, we found that this reflects a direct action of OX40 expressed by CD8 T cells. Furthermore, CD8 T cells that can protect against lethal VACV challenge do not develop in mice deficient in OX40. Thus, OX40, which has been found to play little if any role in the generation of CD8 T cells to several viruses, including lymphocytic choriomeningitis virus and influenza, plays a dominant role in shaping the CD8 T cell response to VACV. These data suggest that unique costimulatory pathways might control alternate antiviral CD8 responses, demonstrating the plasticity of the immune response in utilizing different mechanisms to achieve similar ultimate goals.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants CA91837 and AI67341 (to M.C.), AI77079 (to S.S.-A.), AI56268 and HHSN266200400124C (to A.S.), and a Pew Scholar Award and National Institutes of Health Grant AI63107 (to S.C.).

² This is publication no. 864 from the La Jolla Institute for Allergy and Immunology.

³ Address correspondence and reprint requests to Dr. Michael Croft and Dr. Shahram Salek-Ardakani, Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, San Diego, CA 92037. E-mail addresses: ssalek{at}liai.org; mick{at}liai.org

⁴ Abbreviations used in this paper: IFN-I, tope I IFN; LCMV, lymphocytic choriomeningitis virus; VACV, vaccinia virus; WT, wild type.

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The JI 2008 181: 7433-7434. [Full Text]  

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				Y. Zhao, C. De Trez, R. Flynn, C. F. Ware, M. Croft, and S. Salek-Ardakani The Adaptor Molecule MyD88 Directly Promotes CD8 T Cell Responses to Vaccinia Virus J. Immunol., May 15, 2009; 182(10): 6278 - 6286. [Abstract] [Full Text] [PDF]