The role of gamma interferon in DNA vaccine-induced tumor immunity targeting simian virus 40 large tumor antigen
The central role of CD4+ T lymphocytes in mediating DNA vaccine-induced tumor immunity against the viral oncoprotein simian virus 40 (SV40) large tumor antigen (Tag) has previously been described by our laboratory. In the present study, we extend our previous findings by examining the roles of IFN-γ and Th1-associated effector cells within the context of DNA immunization in a murine model of pulmonary metastasis. Immunization of BALB/c mice with plasmid DNA encoding SV40 Tag (pCMV-Tag) generated IFN-γ-secreting T lymphocytes that produced this cytokine upon in vitro stimulation with mKSA tumor cells. The role of IFN-γ as a mediator of protection against mKSA tumor development was assessed via in vivo IFN-γ neutralization, and these experiments demonstrated a requirement for this cytokine in the induction immune phase. Neutralization of IFN-γ was associated with a reduction in Th1 cytokine-producing CD4+ and CD8+ splenocytes, as assessed by flow cytometry analysis, and provided further evidence for the role of CD4+ T lymphocytes as drivers of the cellular immune response. Depletion of NK cells and CD8+ T lymphocytes demonstrated the expendability of these cell types individually, but showed a requirement for a resident cytotoxic cell population within the immune effector phase. Our findings demonstrate the importance of IFN-γ in the induction of protective immunity stimulated by pCMV-Tag DNA-based vaccine and help to clarify the general mechanisms by which DNA vaccines trigger immunity to tumor cells.
KeywordsDNA vaccine Tumor immunology IFN-γ SV40 large tumor antigen
This work was supported, in part, by National Institutes of Health grant no. RR-12317 and the Office of Research at Texas Tech University Health Sciences Center. J. F. Aldrich is a recipient of the TTUHSC Dean’s Scholars Award and the Mary Lou Clements-Mann Endowed Scholarship. This manuscript is dedicated to the memory of Dr. Ronald C. Kennedy, whose insights and guidance continue to inspire the work of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
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