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¹ Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany
² Laboratory of Immunology, National Institutes of Health, Rockville, MD 20582
³ Institute of Immunology, Free University Berlin, 12200 Berlin, Germany

Address correspondence to Thomas Schüler, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092 Berlin, Germany. Phone: 49-30-9406-2687; Fax: 49-30-9406-2453; E-mail: tschue{at}mdc-berlin.de

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.

Key Words: tumor vaccination • cytotoxic T lymphocytes • interleukin 4 • interleukin 4 (receptor)–deficient mice • cross-priming

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