JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01512-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

TUMOR IMMUNITY AGAINST AN SV40 ONCOPROTEIN REQUIRES CD8+ T LYMPHOCYTES IN THE EFFECTOR IMMUNE PHASE

Devin B. Lowe, Michael H. Shearer, Cynthia A. Jumper, Robert K. Bright, and Ronald C. Kennedy^*

Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX; Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX; Southwest Cancer Treatment and Research Center, Lubbock, TX

^* To whom correspondence should be addressed. Email: ronald.kennedy{at}ttuhsc.edu.

The required activities of CD4+ T cells and antibody against the viral encoded oncoprotein, SV40 Tag, have been previously demonstrated by our laboratory as mediators in achieving anti-tumor responses and tumor protection through antibody-dependent cell-mediated cytotoxicity (ADCC). In this study, we further characterize the necessary immune cell components that lead to systemic tumor immunity within an experimental pulmonary metastatic model as the result of SV40 Tag immunization and antibody production. Immunized animals depleted of CD8+ T cells at the onset of experimental tumor cell challenge developed lung tumor foci and had an overall decreased survival due to lung tumor burden, suggesting a role for CD8+ T cells in the effector phase of the immune response. Lymphocytes and splenocytes harvested from SV40 Tag immunized mice experimentally inoculated with tumor cells synthesized increased in vitro levels of the Th1 cytokine, IFN-, when assessed by ELISA and flow cytometry assays. CD8+ T cell activity was also heightened in SV40 Tag immunized and tumor cell challenged mice based upon intracellular production of perforin, confirming the cytolytic properties of CD8 + T cells against the tumor cell challenge. Altogether, these data point to the role of recombinant SV40 Tag protein immunization in initiating a CTL response during tumor cell dissemination and growth. The downstream activity of CD8+ T cells within this model is likely initiated from SV40 Tag-specific antibody mediating ADCC tumor cell destruction.