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Generation of tumor-associated cytotoxic T lymphocytes requires interleukin 4 from CD8+ T cells

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Item Type:Article
Title:Generation of tumor-associated cytotoxic T lymphocytes requires interleukin 4 from CD8+ T cells
Creators Name:Schueler, T. and Kammertoens, T. and Preiss, S. and Debs, P. and Noben-Trauth, N. and Blankenstein, T.
Abstract:Activation of tumor-associated CD8(+) cytotoxic T lymphocytes (CTLs) often requires antigen representation, e.g., by dendritic cells (DCs), and CD4(+) T cell help. Previously, we showed that CTL-mediated tumor immunity required interleukin 4 (IL-4) during the immunization but not effector phase. To determine the source and target cells of IL-4, we performed adoptive T cell transfers using CD4(+) and CD8(+) T cells from IL-4(-/-) and IL-4R(-/-) mice and analyzed CTL generation. Even though necessary for CTL generation, CD4(+) T cells did not need to express IL-4 or IL-4R. Surprisingly, CTL generation required IL-4 but not IL-4R expression by CD8(+) T cells. As IL-4 (a) was expressed by naive CD8(+) T cells within 24 h after antigen encounter, (b) IL-4 induced DC maturation, and (c) CTL development was impaired in T cell-reconstituted IL-4R(-/-) mice, CD8(+) T cell-derived IL-4 appears to act on DCs. We conclude that CD4(+) and CD8(+) T cells provide different signals for DC activation during CTL generation.
Keywords:Tumor Vaccination, Cytotoxic T Lymphocytes, Interleukin 4, Interleukin 4 (Receptor)–Deficient Mice, Cross-Priming, Animals, Mice
Source:Journal of Experimental Medicine
Publisher:Rockefeller University Press
Page Range:1767-1775
Date:17 December 2001
Official Publication:https://doi.org/10.1084/jem.194.12.1767
PubMed:View item in PubMed

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