Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells
| Autor: | Sven Brandau, Tim Sparwasser, Simone Schimmer, Petra Altenhoff, Gennadiy Zelinskyy, Ulf Dittmer, Ilseyar Akhmetzyanova |
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| Přispěvatelé: | Institute for Virology, University of Duisburg-Essen, Virchowstr 179, 45147, Essen, Germany, ilseyar.akhmetzyanova@uni-due.de. |
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic Male Cancer Research Viral oncogenesis Immunology Medizin Mice Transgenic CD8-Positive T-Lymphocytes Biology Granzymes GZMB Mice Interleukin 21 Effector CD4+ T cells Cell Line Tumor Tumor immunity Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell ZAP70 Regulatory T cells Natural killer T cell Friend murine leukemia virus Mice Inbred C57BL Oncology Cancer research Interleukin 12 Cytokines Female Original Article Leukemia Erythroblastic Acute T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Immunology, Immunotherapy |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1007/s00262-012-1329-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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