Generation of Tumor-associated Cytotoxic T Lymphocytes Requires Interleukin 4 from CD8+ T Cells

T Schüler, T Kammertoens, S Preiss, P Debs… - The Journal of …, 2001 - rupress.org
T Schüler, T Kammertoens, S Preiss, P Debs, N Noben-Trauth, T Blankenstein
The Journal of experimental medicine, 2001rupress.org
Activation of tumor-associated CD8+ cytotoxic T lymphocytes (CTLs) often requires antigen
representation, eg, 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 …
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.
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