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01-10-2007 | Original Article

Interleukin-4 impairs granzyme-mediated cytotoxicity of Simian virus 40 large tumor antigen-specific CTL in BALB/c mice

Authors: Nikola Baschuk, Olaf Utermöhlen, Roland Gugel, Gabriele Warnecke, Ulrike Karow, Daniela Paulsen, Frank Brombacher, Martin Krönke, Wolfgang Deppert

Published in: Cancer Immunology, Immunotherapy | Issue 10/2007

Abstract

In this report we analyzed the impact of interleukin-4 (IL-4) on tumor-associated simian virus 40 (SV40) large T-antigen (TAg)-specific CD8⁺ cytotoxic T cells during rejection of syngeneic SV40 transformed mKSA tumor cells in BALB/c mice. Strikingly, challenge of naïve mice with low doses of mKSA tumor cells revealed a CD8⁺ T cell-dependent prolonged survival time of naïve IL-4^−/− mice. In mice immunized with SV40 TAg we observed in IL-4^−/− mice, or in wild type mice treated with neutralizing anti-IL-4 monoclonal antibody, a strongly enhanced TAg-specific cytotoxicity of tumor associated CD8⁺ T cells. The enhanced cytotoxicity in IL-4^−/− mice was accompanied by a significant increase in the fraction of CD8⁺ tumor associated T-cells expressing the cytotoxic effector molecules granzyme A and B and in granzyme B-specific enzymatic activity. The data suggest that endogenous IL-4 can suppress the generation of CD8⁺ CTL expressing cytotoxic effector molecules especially when the antigen induces only a very weak CTL response.

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Title: Interleukin-4 impairs granzyme-mediated cytotoxicity of Simian virus 40 large tumor antigen-specific CTL in BALB/c mice
Authors: Nikola Baschuk
Olaf Utermöhlen
Roland Gugel
Gabriele Warnecke
Ulrike Karow
Daniela Paulsen
Frank Brombacher
Martin Krönke
Wolfgang Deppert
Publication date: 01-10-2007
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 10/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0309-0

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