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- Title
Tumor-specific CD4 T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.
- Authors
Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf
- 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.
- Subjects
CYTOTOXIC T cells; CANCER cells; RETROVIRUSES; CELL lines; CARCINOGENESIS; TUMOR growth; LABORATORY mice
- Publication
Cancer Immunology, Immunotherapy, 2013, Vol 62, Issue 2, p257
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-012-1329-y