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Tumor-specific CD4(+) T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.
Akhmetzyanova, Ilseyar Zelinskyy, Gennadiy Schimmer, Simone Brandau, Sven Altenhoff, Petra Sparwasser, Tim Dittmer, Ulf
Akhmetzyanova, Ilseyar
Zelinskyy, Gennadiy
Schimmer, Simone
Brandau, Sven
Altenhoff, Petra
Sparwasser, Tim
Dittmer, Ulf
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2013-02
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Abstract
The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.
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Tumor-specific CD4(+) T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells. 2013, 62 (2):257-71 Cancer Immunol. Immunother.
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en
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1432-0851
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Archived with thanks to Cancer immunology, immunotherapy : CII