Tumor-specific CD4(+) T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/271705
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.
Affiliation:
Institute for Virology, University of Duisburg-Essen, Virchowstr 179, 45147, Essen, Germany, ilseyar.akhmetzyanova@uni-due.de.
Citation:
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.
Journal:
Cancer immunology, immunotherapy : CII
Issue Date:
Feb-2013
URI:
http://hdl.handle.net/10033/271705
DOI:
10.1007/s00262-012-1329-y
PubMed ID:
22890822
Type:
Article
Language:
en
ISSN:
1432-0851
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorAkhmetzyanova, Ilseyaren_GB
dc.contributor.authorZelinskyy, Gennadiyen_GB
dc.contributor.authorSchimmer, Simoneen_GB
dc.contributor.authorBrandau, Svenen_GB
dc.contributor.authorAltenhoff, Petraen_GB
dc.contributor.authorSparwasser, Timen_GB
dc.contributor.authorDittmer, Ulfen_GB
dc.date.accessioned2013-03-11T15:15:13Z-
dc.date.available2013-03-11T15:15:13Z-
dc.date.issued2013-02-
dc.identifier.citationTumor-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.en_GB
dc.identifier.issn1432-0851-
dc.identifier.pmid22890822-
dc.identifier.doi10.1007/s00262-012-1329-y-
dc.identifier.urihttp://hdl.handle.net/10033/271705-
dc.description.abstractThe 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Cancer immunology, immunotherapy : CIIen_GB
dc.titleTumor-specific CD4(+) T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.en
dc.typeArticleen
dc.contributor.departmentInstitute for Virology, University of Duisburg-Essen, Virchowstr 179, 45147, Essen, Germany, ilseyar.akhmetzyanova@uni-due.de.en_GB
dc.identifier.journalCancer immunology, immunotherapy : CIIen_GB
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